<SEC-DOCUMENT>0000874015-18-000128.txt : 20181106
<SEC-HEADER>0000874015-18-000128.hdr.sgml : 20181106
<ACCEPTANCE-DATETIME>20181106144610
ACCESSION NUMBER:		0000874015-18-000128
CONFORMED SUBMISSION TYPE:	10-Q
PUBLIC DOCUMENT COUNT:		64
CONFORMED PERIOD OF REPORT:	20180930
FILED AS OF DATE:		20181106
DATE AS OF CHANGE:		20181106

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:		181162602

	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>
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<DESCRIPTION>IONIS PHARMACEUTICALS INC 10-Q 9-30-2018
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 UNITED STATES</div>

<div style="FONT-SIZE: 18pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">SECURITIES AND EXCHANGE COMMISSION</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Washington, DC 20549</div>

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<div style="FONT-SIZE: 18pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Form 10-Q</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">(Mark One)</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">For the Quarterly Period Ended September 30, 2018</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">OR</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF SECURITIES EXCHANGE ACT OF 1934</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">For the transition period from to</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Commission file number 0-19125</div>

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<div style="FONT-SIZE: 18pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Ionis Pharmaceuticals, Inc.</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">(Exact name of Registrant as specified in its charter)</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Delaware</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">33-0336973</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">(State or other jurisdiction of<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif"><br>
</font> incorporation or organization)</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">(IRS Employer Identification No.)</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; TEXT-ALIGN: center">2855 Gazelle Court, Carlsbad, CA</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; TEXT-ALIGN: center">92010</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">(Address of Principal Executive Offices)</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">(Zip Code)</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">760-931-9200</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">(Registrant&#8217;s telephone number, including area code)</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Securities registered pursuant to Section 12(b) of the Act:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">Title of each class</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">Name of each exchange on which registered</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">Common Stock, $.001 Par Value</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">The Nasdaq Stock Market, LLC</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; TEXT-INDENT: 18pt">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></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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">&#61560;</font> No <font style="FONT-SIZE: 10pt; FONT-FAMILY: Wingdings">&#61551;</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T (&#167;232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes <font style="FONT-SIZE: 10pt; FONT-FAMILY: Wingdings">&#61560;</font> No<font style="FONT-SIZE: 10pt; FONT-FAMILY: Wingdings">&#61551;</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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):</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">Large accelerated filer <font style="FONT-SIZE: 10pt; FONT-FAMILY: Wingdings">&#61560;</font></div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">Accelerated filer <font style="FONT-SIZE: 10pt; FONT-FAMILY: Wingdings">&#61551;</font></div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">Non-accelerated filer <font style="FONT-SIZE: 10pt; FONT-FAMILY: Wingdings">&#61551;</font></div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">Smaller reporting company <font style="FONT-SIZE: 10pt; FONT-FAMILY: Wingdings">&#61551;</font></div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">(Do not check if a smaller reporting company)</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">Emerging growth company <font style="FONT-SIZE: 10pt; FONT-FAMILY: Wingdings">&#61551;</font></div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; TEXT-INDENT: 36pt">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">&#61551;</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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">&#61551;</font> No <font style="FONT-SIZE: 10pt; FONT-FAMILY: Wingdings">&#61560;</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">The number of shares of voting common stock outstanding as of October 31, 2018 was 137,571,510.

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">IONIS PHARMACEUTICALS, INC.</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">FORM 10-Q</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">INDEX</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">PART I</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">FINANCIAL INFORMATION</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">ITEM 1:</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Financial Statements:</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10.35pt">Condensed Consolidated Balance Sheets as of September 30, 2018 and December 31, 2017 (unaudited) (as revised)</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">3</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10.35pt">Condensed Consolidated Statements of Operations for the three and nine months ended September 30, 2018 and 2017 (unaudited) (as revised)</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">4</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10.35pt">Condensed Consolidated Statements of Comprehensive Income (Loss) for the three and nine months ended September 30, 2018 and 2017 (unaudited) (as revised)</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">5</div>
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<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10.35pt">Condensed Consolidated Statements of Cash Flows for the nine months ended September 30, 2018 and 2017 (unaudited) (as revised)</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">6</div>
</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; TEXT-INDENT: 10.35pt">Notes to Condensed Consolidated Financial Statements (unaudited)</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">7</div>
</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">ITEM 2:</div>
</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations:</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10.35pt">Overview</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">31</div>
</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10.35pt">Results of Operations</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">40</div>
</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10.35pt">Liquidity and Capital Resources</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">45</div>
</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">ITEM 3:</div>
</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Quantitative and Qualitative Disclosures about Market Risk</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">47</div>
</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">ITEM 4:</div>
</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Controls and Procedures</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">47</div>
</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">PART II</div>
</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">OTHER INFORMATION</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">48</div>
</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">ITEM 1:</div>
</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Legal Proceedings</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">48</div>
</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">
<div>&#160;</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">ITEM 1A:</div>
</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">
<div>&#160;</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Risk Factors</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">48</div>
</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div>&#160;</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">ITEM 2:</div>
</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div>&#160;</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Unregistered Sales of Equity Securities and Use of Proceeds</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">57</div>
</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">ITEM 3:</div>
</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Default upon Senior Securities</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">57</div>
</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">ITEM 4:</div>
</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Mine Safety Disclosures</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">57</div>
</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">ITEM 5:</div>
</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Other Information</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">57</div>
</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">ITEM 6:</div>
</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Exhibits</div>
</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">58</div>
</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 13.69%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">SIGNATURES</div>
</td>
<td style="WIDTH: 78.3%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 8%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">59</div>
</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">TRADEMARKS</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold">&#160;</font>"Ionis," the Ionis logo, and other trademarks or service marks of Ionis Pharmaceuticals,&#160;Inc. appearing in this report are the property of Ionis Pharmaceuticals, Inc. "Akcea," the Akcea logo, and other trademarks or service marks appearing in this report, including 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.</div>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">2</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">IONIS PHARMACEUTICALS, INC.</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">CONDENSED CONSOLIDATED BALANCE SHEETS</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(in thousands, except share data)</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(Unaudited)</div>

<div><br>
</div>

<table id="zb9f7675724934953ab967ae8aef1452d" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center; TEXT-INDENT: 4.5pt">December 31,</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(as revised*)</div>
</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">ASSETS</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Current assets:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Cash and cash equivalents</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">479,891</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">129,630</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Short-term investments</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,479,098</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">893,085</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Contracts receivable</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">14,732</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">62,955</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Inventories</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">8,378</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">9,982</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Other current assets</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">97,125</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">73,082</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Total current assets</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,079,224</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,168,734</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Property, plant and equipment, net</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">132,003</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">121,907</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Patents, net</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">24,027</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">22,004</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Deposits and other assets</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12,659</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,129</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 54pt; TEXT-INDENT: -9pt">Total assets</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,247,913</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,322,774</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">LIABILITIES AND STOCKHOLDERS&#8217; EQUITY</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Current liabilities:</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Accounts payable</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">13,576</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">24,886</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Accrued compensation</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">24,259</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">25,151</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Accrued liabilities</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">50,786</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">66,618</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Current portion of long-term obligations</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">14,472</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,621</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Current portion of deferred contract revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">157,145</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">125,336</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total current liabilities</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">260,238</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">243,612</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Long-term deferred contract revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">523,384</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">108,026</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">1 percent convertible senior notes</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">559,184</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">533,111</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Long-term obligations, less current portion</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,138</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12,974</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Long-term mortgage debt</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">59,825</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">59,771</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Total liabilities</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,407,769</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">957,494</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Stockholders&#8217; equity:</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Common stock, $0.001 par value; 300,000,000 shares authorized, 137,506,203 and 124,976,373 shares issued and outstanding at September 30, 2018 and December 31, 2017, respectively</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">138</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">125</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Additional paid-in capital</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,030,313</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,553,681</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Accumulated other comprehensive loss</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(32,532</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(31,759</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Accumulated deficit</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,287,369</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,241,034</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Total Ionis stockholders&#8217; equity</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">710,550</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">281,013</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">&#160;&#160;&#160;Noncontrolling interest in Akcea Therapeutics, Inc.</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">129,594</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">84,267</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Total stockholders&#8217; equity</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">840,144</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">365,280</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 54pt; TEXT-INDENT: -9pt">Total liabilities and stockholders&#8217; equity</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,247,913</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,322,774</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">* Our 2017 amounts are revised to reflect the new revenue recognition accounting guidance, which we adopted retrospectively in the first quarter of 2018. Refer to Note 2, <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic">Significant Accounting Policies</font>, for further information.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">See accompanying notes.</div>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">3</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">IONIS PHARMACEUTICALS, INC.</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(in thousands, except for per share amounts)</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(Unaudited)</div>

<div><br>
</div>

<table id="z0b403c4502a640bfaae9c62442951e0b" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold">(as revised*)</font> </div>
</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold">(as revised*)</font> </div>
</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Commercial revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 45pt; TEXT-INDENT: -27pt">SPINRAZA royalties</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">70,010</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">32,890</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">167,743</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">60,467</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 45pt; TEXT-INDENT: -27pt">Licensing and other royalty revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12,746</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,727</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">14,232</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,639</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 45pt; TEXT-INDENT: -9pt">Total commercial revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">82,756</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">34,617</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">181,975</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">66,106</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Research and development revenue under collaborative agreements</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">62,639</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">83,697</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">225,584</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">280,281</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -9pt">Total revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">145,395</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">118,314</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">407,559</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">346,387</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Expenses:</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Research, development and patent</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">95,255</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">80,214</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">301,153</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">246,358</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Selling, general and administrative</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">68,712</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">26,788</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">178,563</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">62,782</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -9pt">Total operating expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">163,967</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">107,002</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">479,716</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">309,140</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -9pt">Income (loss) from operations</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(18,572</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,312</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(72,157</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">37,247</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Other income (expense):</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Investment income</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">9,963</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,811</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">18,711</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">7,504</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Interest expense</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(11,282</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(10,825</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(33,332</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(33,966</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Loss on extinguishment</font> of financing liability for leased facility</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,689</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,689</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Other income (expenses)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(22</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2,141</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(145</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(3,528</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
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</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Loss before income tax expense</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(19,913</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(6,532</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(86,923</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(432</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
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<tr>
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</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Income tax expense</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(452</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(961</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(824</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,184</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
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</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net loss</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(20,365</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,493</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(87,747</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,616</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
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<tr>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
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</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left">Net loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">15,806</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4,882</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">41,412</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4,882</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
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</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(4,559</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2,611</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(46,335</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,266</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Basic net income (loss) per share</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.03</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.02</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.33</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.13</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Shares used in computing basic net income (loss) per share</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">143,314</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">124,370</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">132,518</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">123,746</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Diluted net income (loss) per share</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.03</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.02</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.33</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.13</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Shares used in computing diluted net income (loss) per share</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">143,314</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">124,370</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">132,518</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">125,858</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">* Our 2017 amounts are revised to reflect the new revenue recognition accounting guidance, which we adopted retrospectively in the first quarter of 2018. Refer to Note 2, <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic">Significant Accounting Policies</font>, for further information.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">&#160;See accompanying notes.</div>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">4</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">IONIS PHARMACEUTICALS, INC.</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS)</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(in thousands)</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(Unaudited)</div>

<div><br>
</div>

<table id="z8557b2f4e8cb4e8b9129a9ba3626f5af" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
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<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
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<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: right">(as revised*)</div>
</td>
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<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: right">(as revised*)</div>
</td>
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</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net loss</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(20,365</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,493</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(87,747</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,616</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
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<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Unrealized gains (losses) on debt securities, net of tax</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">133</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">215</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(834</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">610</div>
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</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Reclassification adjustment for realized gains included in net income (loss)</div>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(374</div>
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</td>
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<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Currency translation adjustment</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(28</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">61</div>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(77</div>
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</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Comprehensive loss</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(20,260</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,320</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(88,520</div>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,457</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
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</td>
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</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Comprehensive loss attributable to noncontrolling interests</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">15,797</div>
</td>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,952</div>
</td>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">41,455</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,952</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
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</tr>

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<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Comprehensive income (loss) attributable to Ionis Pharmaceuticals, Inc. stockholders</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(4,463</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(3,368</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(47,065</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,495</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">&#160;</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">* Our 2017 amounts are revised to reflect the new revenue recognition accounting guidance, which we adopted retrospectively in the first quarter of 2018. Refer to Note 2, <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic">Significant Accounting Policies</font>, for further information.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">See accompanying notes.</div>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">5</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">IONIS PHARMACEUTICALS, INC.</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(in thousands)</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(Unaudited)</div>

<div><br>
</div>

<table id="z31e6882239d3419f893515a4cb6b7d5a" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Operating activities:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(as revised*)</div>
</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net loss</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(87,747</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,616</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Adjustments to reconcile net loss to net cash provided by operating activities:</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Depreciation</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">7,650</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">6,138</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Amortization of patents</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,356</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,216</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Amortization of premium on investments, net</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">791</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,227</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Amortization of debt issuance costs</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,343</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,202</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Amortization of convertible senior notes discount</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">24,781</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">22,963</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Amortization of long-term financing liability for leased facility</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,659</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Stock-based compensation expense</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">97,210</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">63,642</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Gain on investment in Regulus Therapeutics, Inc.</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(374</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Loss on extinguishment of financing liability for leased facility</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">7,689</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Non-cash losses related to patents, licensing and property, plant and equipment</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">482</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(403</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Changes in operating assets and liabilities:</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Contracts receivable</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">48,223</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">65,119</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Inventories</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,604</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(962</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Other current and long-term assets</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(26,573</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(34,866</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Accounts payable</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(13,606</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,707</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Accrued compensation</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(892</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(8,999</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Accrued liabilities and deferred rent</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(14,392</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(5,251</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Deferred contract revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">447,168</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">31,071</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 54pt; TEXT-INDENT: -9pt">Net cash provided by operating activities</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">487,398</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">153,748</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Investing activities:</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Purchases of short-term investments</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,156,335</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(589,655</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Proceeds from the sale of short-term investments</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">568,517</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">313,860</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Purchases of property, plant and equipment</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(12,221</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(26,502</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Acquisition of licenses and other assets, net</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(3,317</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(4,289</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Proceeds from the sale of Regulus Therapeutics stock</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,507</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 54pt; TEXT-INDENT: -9pt">Net cash used in investing activities</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(603,356</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(304,079</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Financing activities:</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Proceeds from equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">18,254</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">17,672</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -8.9pt">Proceeds from the issuance of common stock from Akcea Therapeutics, Inc.&#8217;s initial public offering, net of underwriters&#8217; discount</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">110,438</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Proceeds from building mortgage debt, net of issuance costs</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">59,750</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Proceeds from the issuance of common stock to Novartis</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">71,737</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Proceeds from the issuance of common stock to Biogen</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">447,965</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Offering costs paid</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,057</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Proceeds from the sale of Akcea Therapeutics, Inc. common stock to Novartis in a private placement</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">50,000</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Payment to settle financing liability for leased facility</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(80,133</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Principal payments on debt and capital lease obligations</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(3,577</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 54pt; TEXT-INDENT: -9pt">Net cash provided by financing activities</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">466,219</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">224,830</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net increase in cash and cash equivalents</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">350,261</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">74,499</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Cash and cash equivalents at beginning of period</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">129,630</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">84,685</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Cash and cash equivalents at end of period</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">479,891</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">159,184</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Supplemental disclosures of cash flow information:</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Interest paid</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,434</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4,020</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Supplemental disclosures of non-cash investing and financing activities:</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Amounts accrued for capital and patent expenditures</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,296</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,475</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Purchases of property, plant and equipment included in long-term obligations</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,596</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 76%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -9pt">Unpaid deferred offering costs</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">638</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">* Our 2017 amounts are revised to reflect the new revenue recognition accounting guidance, which we adopted retrospectively in the first quarter of 2018. Refer to Note 2, <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic">Significant Accounting Policies</font>, for further information.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">See accompanying notes.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">IONIS PHARMACEUTICALS, INC.</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">NOTES TO CONDENSED CONSOLIDATED FINANCIAL STATEMENTS</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30, 2018</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(Unaudited)</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">1.&#160; Basis of Presentation</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended September 30, 2018 and 2017 on the same basis as the audited financial statements for the year ended December 31, 2017. 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, 2017 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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, which we formed in December 2014. </font>Prior to Akcea&#8217;s <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">initial public offering, or IPO,</font> 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 <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">68 percent </font>of Akcea. In the second and third 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. We reflected the increase in our ownership in these financial statements. In October 2018, we received an additional 1.7 million shares of Akcea&#8217;s stock when TEGSEDI received marketing authorization in the U.S., increasing our ownership to approximately 76 percent. <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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; COLOR: #000000; FONT-STYLE: italic">Significant Accounting Policies,</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> for further information related to our accounting for our investment in Akcea.</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">2.&#160; Significant Accounting Policies</div>

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</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Revenue Recognition</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><u>Adoption of New Revenue Recognition Accounting Standard (Topic 606)</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In May 2014, the FASB issued accounting guidance on the recognition of revenue from customers. <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">This guidance supersedes the revenue recognition requirements we previously followed in Accounting Standards Codification, or ASC, Topic 605, </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic">Revenue Recognition</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">, or Topic 605, and created a new Topic 606, </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic">Revenue from Contracts with Customers</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">, or Topic 606. </font>Under Topic 606, an entity will recognize revenue when it transfers control of promised goods or services to customers in an amount that reflects what the entity expects to receive in exchange for the goods or services. Further, an entity will recognize revenue upon satisfying the performance obligation(s) under the related contract. We adopted Topic 606 on January 1, 2018 under the full retrospective approach, which required us to revise our prior period revenue. Under Topic 606, we were required to review all of our ongoing collaboration agreements in which we recognized revenue after January 1, 2016. We were required to assess what our revenue would have been for the period from January 1, 2016 to December 31, 2017 under Topic 606. As a result of this analysis, we determined that the cumulative revenue we would have recognized under Topic 606 decreased by $53.6 million. We recorded this amount as a cumulative adjustment to our accumulated deficit as of December 31, 2017. We have labeled our prior period financial statements &#8220;as revised&#8221; to indicate the change required under the accounting rules.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following tables summarize the adjustments we were required to make to amounts we originally reported in 2017 to adopt Topic 606 (in thousands, except per share amounts):</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Condensed Consolidated Balance Sheet</div>

<div><br>
</div>

<table id="zd05da368765e42259d248681facc2c37" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="10">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">At December 31, 2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Previously</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Reported under</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 605</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 606</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Adjustment</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Revised</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Current portion of deferred revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">106,465</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">18,871</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">125,336</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Long-term portion of deferred revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">72,708</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">35,318</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">108,026</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Accumulated deficit</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,187,398</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(53,636</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,241,034</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;&#160;&#160;Noncontrolling interest in Akcea Therapeutics, Inc.</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">87,847</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(3,580</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">84,267</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Total stockholders&#8217; equity</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">418,719</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(53,439</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">365,280</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">7</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Condensed Consolidated Statement of Operations</div>

<div><br>
</div>

<table id="z74551ac492074f6bb2e3b64df79d27f3" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="10">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended September 30, 2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Previously</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Reported under</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 605</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 606</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Adjustment</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Revised</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Commercial revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: 8.85pt">SPINRAZA royalties</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">32,890</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">32,890</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: 8.85pt">Licensing and other royalty revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">879</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">848</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,727</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: 17.75pt">Total commercial revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">33,769</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">848</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">34,617</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Research and development revenue under collaborative agreements</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">87,142</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(3,445</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">83,697</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -9pt">Total revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">120,911</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2,597</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">118,314</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr style="HEIGHT: 16px">
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Income (loss) from operations</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">13,909</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2,597</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,312</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(4,896</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2,597</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,493</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(976</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,635</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2,611</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss) per share, basic and diluted</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.00</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.02</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.02</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>
</table>

<div><br>
</div>

<table id="z9804af793beb4552b86b15d391aaa2d2" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="10">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended September 30, 2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Previously</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Reported under</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 605</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 606</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Adjustment</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Revised</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Commercial revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: 8.85pt">SPINRAZA royalties</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">60,467</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">60,467</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: 8.85pt">Licensing and other royalty revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4,983</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">656</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,639</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: 17.75pt">Total commercial revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">65,450</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">656</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">66,106</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Research and development revenue under collaborative agreements</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">269,917</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,364</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">280,281</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -9pt">Total revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">335,367</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,020</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">346,387</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Income from operations</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">26,227</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,020</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">37,247</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(12,636</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,020</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,616</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(8,716</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,982</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,266</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss) per share, basic</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.02</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.11</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.13</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss) per share, diluted</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.02</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.11</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.13</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Condensed Consolidated Statement of Cash Flows</div>

<div><br>
</div>

<table id="z706577b4adfa45bf9950e1ce42c6d22d" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="10">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended September 30, 2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Previously</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Reported under</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 605</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 606</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Adjustment</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Revised</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(12,636</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,020</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,616</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Adjustments to reconcile net income (loss) to net cash provided by operating activities:</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -27.15pt">Deferred contract revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">42,091</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(11,020</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">31,071</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Cash and cash equivalents at beginning of period</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">84,685</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">84,685</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Cash and cash equivalents at end of period</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">159,184</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">159,184</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Under Topic 606, compared to Topic 605, our revenue decreased $2.6 million for the three months ended <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">September 30, 2017</font>, and increased $11.0 million for the <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">nine months ended September 30, 2017</font>. The change in our revenue was primarily due to:</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="zb7c6856f7250490093ae3cfa692f945e" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif"><u>A change in how we recognize milestone payments:</u></font> Topic 606 requires us to amortize more of the milestone payments we achieve, rather than recognizing the milestone payments in full in the period in which we achieved the milestone event as we did under Topic 605. This change resulted in an increase of $0.5 million and $27.9 million for the three and nine months ended September 30, 2017, respectively.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif"><u>A change in how we calculate revenue for payments we are recognizing into revenue over time:</u></font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif"> Under Topic 605, we amortized payments into revenue evenly over the period of our obligations. When we made a change to our estimated completion period, we recognized that change on a prospective basis. Under Topic 606, we are required to use an input method to determine the amount we amortize each reporting period. Each period, we review our &#8220;inputs&#8221; such as our level of effort expended, including the time we estimate it will take us to complete the activities, or costs incurred relative to the total expected inputs to satisfy the performance obligation. For certain collaborations, such as Bayer, Janssen and Novartis, the input method resulted in a change to the revenue we had previously recognized using a straight-line amortization method.</font><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">This change resulted in a decrease of $4.0 million and $17.5 million for the three and nine months ended September 30, 2017, respectively.</font></div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our updated revenue recognition policy reflecting Topic 606 is as follows:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><u>Our Revenue Sources</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 condensed consolidated balance sheet.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We expect to add product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 as a result of TEGSEDI&#8217;s approval in the U.S., EU and Canada. We will also recognize as commercial revenue future sales milestone payments and royalties we earn under our partnerships.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Research and development revenue under collaborative agreements</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our collaboration agreements are detailed in Note 6, <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic">Collaborative Arrangements and Licensing Agreements.</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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><u>Steps to Recognize Revenue</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We use a five step process to determine the amount of revenue we should recognize and when we should recognize it. The five step process is as follows:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic">Identify the contract</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left; TEXT-INDENT: 36pt">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We and our partner approved the contract and we are both committed to perform our obligations;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We have identified our rights, our partner&#8217;s rights and the payment terms;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We believe collectability is probable.</div>
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; align: right">2.</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic">Identify the performance obligations</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Often times when we enter into a collaboration agreement in which we provide our partner with an option to license a drug 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 drug 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 drug or requests additional goods or services, then we identify a new performance obligation for that item.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="TEXT-ALIGN: justify">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic">Determine the transaction price</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="TEXT-ALIGN: justify">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; align: right">4.</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic">Allocate the transaction price</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Estimated future product sales;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Estimated royalties on future product sales;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Contractual milestone payments;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Expenses we expect to incur;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Income taxes; and</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">A discount rate.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We typically estimate the selling price of R&amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;D services include:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">The number of internal hours we estimate we will spend performing these services;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">The estimated cost of work we will perform;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">The estimated cost of work that we will contract with third parties to perform; and</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">The estimated cost of API we will use.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">For purposes of determining the stand-alone selling price of the R&amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic">Recognize revenue</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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; COLOR: #000000">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></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left; TEXT-INDENT: 36pt">The following are examples of when we typically recognize revenue based on the types of payments we receive.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic; TEXT-ALIGN: left; TEXT-INDENT: 36pt"><u>Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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. Our accounting for SPINRAZA royalties did not change as a result of adopting Topic 606.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic; TEXT-ALIGN: left; TEXT-INDENT: 36pt"><u>Research and development revenue under collaboration agreements:</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic; TEXT-ALIGN: left; TEXT-INDENT: 36pt"><u>Upfront Payments</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 new SMA collaboration with Biogen, we received a $25 million upfront payment in December 2017. We allocated the upfront payment to our single performance obligation, R&amp;D services. We are amortizing the $25 million upfront payment using an input method over the estimated period of time we are providing R&amp;D services. Refer to <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Note 6, </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic">Collaborative Arrangements and Licensing Agreements</font>, for further discussion. Under Topic 605, we amortized upfront payments evenly over the period of our obligation.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><u>Milestone Payments</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 drug is approved by the applicable regulator. We will recognize sales based milestone payments in the period we achieve the milestone under the sales-based royalty exception allowed under accounting rules.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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. Under Topic 606, we allocated this payment to our R&amp;D services performance obligation. We are recognizing revenue from this milestone payment over our estimated period of performance. Under Topic 605, this milestone payment was recognized in full in the third quarter of 2017, which was the period in which we achieved the milestone event.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the milestone event. For example, in the third quarter of 2018, we earned a $10 million milestone payment when AstraZeneca initiated a Phase 1 study of IONIS-AZ4-2.5-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>. Our revenue recognition of milestone payments we earn based on our partners&#8217; activities did not change as a result of adopting Topic 606.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><u>License Fees</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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 third quarter of 2018, we earned a $12 million license fee when our majority-owned affiliate, Akcea, <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">entered into an exclusive license agreement with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America</font>. Our recognition of license fees did not change as a result of adopting Topic 606.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Amendments to Agreements</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:</div>

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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">1)</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div>
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">2)</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">If the goods and/or services are at a stand-alone selling price.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 standalone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> 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;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> 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;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> and to initiate development of IONIS-FXI-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">, 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;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> and IONIS-FXI-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">. 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;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">, 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; COLOR: #000000">Note 6, </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic">Collaborative Arrangements and Licensing Agreements</font>, for further discussion <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">of our accounting treatment for our Bayer collaboration. </font>Our allocation of the consideration we received for the Bayer amendment did not change as a result of adopting Topic 606. However, the method in which we are recognizing revenue related to our R&amp;D services performance obligation did change. We are amortizing revenue related to our R&amp;D services performance obligation using the input method under Topic 606.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Multiple Agreements</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Whether the goods and/or services promised under the agreements are a single performance obligation.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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; COLOR: #000000">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. Refer to Note 6, </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic">Collaborative Arrangements and Licensing Agreements</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> for further discussion of the accounting treatment for the 2018 strategic neurology collaboration with Biogen.</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 54pt; TEXT-INDENT: -18pt">Contracts Receivable</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Our contracts receivable balance represents the amounts we have billed our partners for goods we have delivered or services we have performed that are due to us unconditionally. When we bill our partners 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</font>. Our contracts receivable balance as of December 31, 2017 did not change when we adopted Topic 606.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; MARGIN-LEFT: 54pt; TEXT-INDENT: -18pt">Unbilled SPINRAZA Royalties</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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>Our unbilled SPINRAZA royalties as of December 31, 2017 did not change when we adopted Topic 606.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 54pt; TEXT-INDENT: -18pt">Deferred Revenue</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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 and nine months ended September 30, 2018, we recognized $37.2 million and $80.4 million of revenue from amounts that were in our beginning deferred revenue balances for those periods, respectively. During the three and nine months ended September 30, 2017, we recognized $31.6 million and $84.4 million of revenue from amounts that were in our beginning deferred revenue balances for those periods, respectively. Refer to our revenue recognition policy above detailing how we recognize revenue for further discussion.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following table summarizes the adjustments we were required to make to our deferred revenue amounts to adopt Topic 606 (in thousands):</div>

<div><br>
</div>

<table id="z9f90980cc91b4fee8e584a26ec2ee5c6" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 70%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="11">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">At December 31, 2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Previously</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Reported under</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 605</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 606</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Adjustment</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Revised</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Current portion of deferred revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">106,465</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">18,871</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">125,336</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Long-term portion of deferred revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">72,708</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">35,318</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">108,026</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt">Total deferred revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">179,173</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">54,189</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">233,362</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our deferred revenue balance increased $54.2 million at December 31, 2017 under Topic 606, compared to Topic 605. The increase was primarily related to the change in the accounting for certain milestone payments and the way in which we amortize payments. Under Topic 605, we previously recognized the majority of the milestone payments we earned in the period we achieved the milestone event, which did not impact our deferred revenue balance. Under Topic 606 we are now amortizing more milestone payments over the period of our performance obligation, which adds to our deferred revenue balance. Additionally, under Topic 605 we amortized payments evenly over the period of our obligation. Under Topic 606, we are required to use an input method to determine the amount we amortize each reporting period. The increase in deferred revenue relates to agreements with the following partners:</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z9a4943e92e364ed28a958b3d3c4a0113" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$24.2 million from Biogen;</div>
</td>
</tr>
</table>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z75e39b51334a48c6996e019f2c060775" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$15.9 million from AstraZeneca;</div>
</td>
</tr>
</table>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z741fbd7d99e34706ba4d998c2802d9a5" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$11.8 from Novartis; and</div>
</td>
</tr>
</table>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z956413db8f8d44b2b60ed6c7f4883a33" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$2.3 million from other partners.</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">12</font></div>

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</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Noncontrolling Interest in Akcea Therapeutics, Inc.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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; COLOR: #000000">&#160;</font>of Akcea. In the second and third 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. We reflected this increase in our ownership percentage in these financial statements as an adjustment to noncontrolling interest. In October 2018, we received an additional 1.7 million shares of Akcea&#8217;s stock when TEGSEDI received marketing authorization in the U.S., increasing our ownership to approximately 76 percent. <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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 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></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Cash, cash equivalents and investments</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

<div><br>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At September 30, 2018, we held an equity investment in one publicly held company, 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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In January 2018, we adopted the amended accounting guidance related to the recognition, measurement, presentation, and disclosure of certain financial instruments. The amended guidance requires us to measure and record our equity investments at fair value. Additionally, the amended accounting guidance requires us to recognize the changes in fair value in our consolidated statement of operations, instead of through accumulated other comprehensive income. Prior to 2018, we accounted for our equity investments in privately held companies under the cost method of accounting. Under the amended guidance we account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. Our adoption of this guidance did not have an impact on our results.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Inventory valuation</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We reflect our inventory on our 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 drugs because until we use these raw materials they have alternative future uses. We include in inventory raw material costs for drugs 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 drug. For example, if one of our drugs failed, we could use the raw materials for that drug to manufacture our other drugs. We expense these costs as R&amp;D expenses when we begin to manufacture API for a particular drug if the drug has not been approved for marketing by a regulatory agency.</div>

<div style="TEXT-ALIGN: justify"><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We obtained the first regulatory approval for TEGSEDI in July 2018. At September 30, 2018 and December 31, 2017, 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.</div>

<div><br>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 drugs and historical write-offs. We did not record any inventory write-offs for the nine months ended September 30, 2018 and 2017.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; MARGIN-LEFT: 36pt">Research, development and patent expenses</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our research and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our condensed consolidated balance sheet and we expense them as the services are provided.</div>

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</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">13</font></div>

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</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Long-lived assets</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We evaluate long-lived assets, which include property, plant and equipment 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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Use of estimates</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Basic and diluted net income (loss) per share</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Basic net income (loss) per share</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The calculation of total net income (loss) attributable to our common stockholders for the three and nine months ended September 30, 2018 and 2017 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. As a result of this calculation, our&#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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our basic net loss per share for the three months ended <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">September 30, 2018</font>, was calculated as follows (in thousands, except per share amounts):</div>

<div><br>
</div>

<table id="zefcce3708b884a2590925d8db200dd31" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">Three months ended September 30, 2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Weighted</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Average Shares</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Owned in Akcea</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Akcea&#8217;s</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Net Income (Loss)</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Per Share</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Ionis&#8217; Portion of</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Akcea&#8217;s Net Loss</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: top" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Common shares</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">65,538</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.73</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(47,843</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Akcea&#8217;s net loss attributable to our ownership</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(47,843</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Ionis&#8217; stand-alone net income</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">43,226</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Net loss available to Ionis common stockholders</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(4,616</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Weighted average shares outstanding</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">143,314</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Basic net loss per share</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.03</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>
</table>

<div><br>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Akcea&#8217;s net loss per share calculation for the nine months ended <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">September 30, 2018 included two components: (1) Akcea&#8217;s net loss from its statement of operations and (2) deemed distributions related to the license of </font>TEGSEDI in the second quarter of 2018. Because we own more than 50 percent of Akcea, we and Akcea are under common control.&#160;As such, Akcea accounted for the TEGSEDI transaction using common control guidance.&#160;Accordingly, Akcea recorded the license we granted to them at carrying value.&#160;In addition, Akcea recorded the consideration it paid to us in excess of the carrying value as a deemed distribution.&#160;Accounting rules required Akcea to include these deemed distributions in their net loss per share calculation as if Akcea had paid us a dividend. &#160;&#160;&#160;&#160;&#160;</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our basic net loss per share for the <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">nine months ended September 30, 2018</font>, was calculated as follows (in thousands, except per share amounts):</div>

<div><br>
</div>

<table id="zb21ac3544e05479eb08e8de0c1f62c0e" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">Nine months ended September 30, 2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Weighted</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Average Shares</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Owned in Akcea</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Akcea&#8217;s</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Net Loss</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Per Share</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Ionis&#8217; Portion of</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Akcea&#8217;s Net Loss</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: top" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Common shares</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">57,347</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1.93</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(110,680</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Akcea&#8217;s net loss attributable to our ownership</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(110,680</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Ionis&#8217; stand-alone net income</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">67,517</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Net income available to Ionis common stockholders</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(43,162</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Weighted average shares outstanding</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">132,518</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Basic net loss per share</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.33</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>
</table>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">14</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Prior to Akcea&#8217;s IPO in July 2017, we owned Akcea series A convertible preferred stock, which included a six percent cumulative dividend. Upon completion of Akcea&#8217;s IPO in July 2017, our preferred stock was converted into common stock on a 1:1 basis. The preferred stock dividend was not paid at the IPO because the IPO was not a liquidation event or a change in control. During the three and nine months ended September 30, 2017, Akcea used a two-class method to compute its net income (loss) per share because it had both common and preferred shares outstanding during the periods. The two-class method required Akcea to calculate its net income (loss) per share&#160;for each class of stock by dividing total distributable losses applicable to preferred and common stock, including the&#160;six percent&#160;cumulative dividend contractually due to series A convertible preferred shareholders, by the weighted-average of preferred and common shares outstanding during the requisite period. Since Akcea used the two-class method, accounting rules required us to include our portion of Akcea's net income (loss) per share for both Akcea's common and preferred shares that we owned in our calculation of basic and diluted net income (loss) per share for three and nine months ended September 30, 2017.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our basic net income per share for the three months ended <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">September 30, 2017</font>, was calculated as follows (in thousands, except per share amounts):</div>

<div><br>
</div>

<table id="z40d017f47020495f88e445ec10e51c23" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">Three months ended September 30, 2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Weighted</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Average Shares</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Owned in Akcea</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Akcea&#8217;s</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Net Loss</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Per Share</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Ionis&#8217; Portion of</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Akcea&#8217;s Net Loss</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: top" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Common shares</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">36,556</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.33</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(12,063</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Preferred shares</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,651</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.01</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(57</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Akcea&#8217;s net loss attributable to our ownership</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(12,120</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Ionis&#8217; stand-alone net income</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,144</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Net loss available to Ionis common stockholders</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,976</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Weighted average shares outstanding</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">124,370</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Basic net income per share</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.02</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our basic net income per share for the <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">nine months ended September 30, 2017</font>, was calculated as follows (in thousands, except per share amounts):</div>

<div><br>
</div>

<table id="z724acf2e825e4a4cb682314da44f5184" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">Nine months ended September 30, 2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Weighted</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Average Shares</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Owned in Akcea</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Akcea&#8217;s</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Net Loss</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Per Share</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Ionis&#8217; Portion of</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Akcea&#8217;s Net Loss</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: top" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Common shares</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12,319</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(3.12</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(38,435</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Preferred shares</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">21,055</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2.16</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(45,479</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Akcea&#8217;s net loss attributable to our ownership</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(83,914</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Ionis&#8217; stand-alone net income</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">100,235</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Net income available to Ionis common stockholders</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">16,321</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Weighted average shares outstanding</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">123,746</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Basic net income per share</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.13</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Dilutive net income (loss per share)</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">For the three and nine months ended September 30, 2018 and for the three months ended September 30, 2017, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:</div>

<div><br>
</div>

<div style="TEXT-ALIGN: left">
<table id="z58ec5d8310ce4b2a9eb42c8b55fedcf7" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: left">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1 percent convertible senior notes;</div>
</td>
</tr>
</table>
</div>

<div style="TEXT-ALIGN: left">
<table id="z5f987442b3b447a5a6d7061b681f203b" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: left">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2&#190; percent convertible senior notes;</div>
</td>
</tr>
</table>
</div>

<div style="TEXT-ALIGN: left">
<table id="zc07c0c8ffaae403fa1d3387058278773" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: left">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Dilutive stock options;</div>
</td>
</tr>
</table>
</div>

<div style="TEXT-ALIGN: left">
<table id="z765acdae846b45bd8f39ac89dc7667e1" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: left">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Unvested restricted stock units; and</div>
</td>
</tr>
</table>
</div>

<div style="TEXT-ALIGN: left">
<table id="zbc4431c719c6429ea8e890cbe89ee808" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: left">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Employee Stock Purchase Plan, or ESPP.</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">For the nine months ended September 30, 2017, 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 those periods. Diluted common equivalent shares for the nine months ended September 30, 2017 consisted of the following (in thousands except per share amounts):</div>

<div><br>
</div>

<table id="za5896e7896c144279385b28e6d7f2712" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">Nine months ended September 30, 2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Income</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(Numerator)</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Shares</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(Denominator)</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Per-Share</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Amount</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: top" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income available to Ionis common stockholders</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">16,321</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">123,746</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.13</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Effect of dilutive securities:</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -8.9pt">Shares issuable upon exercise of stock options</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,658</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: 0.1pt">Shares issuable upon restricted stock award issuance</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">430</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; TEXT-INDENT: 9.1pt">Shares issuable related to our ESPP</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">24</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9.1pt; TEXT-INDENT: -9.1pt">Income available to Ionis common stockholders, plus assumed conversions</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">16,321</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">125,858</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.13</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">15</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">For the nine months ended September 30, 2017, the calculation excluded the 1 percent and 2&#190; percent notes because the effect on diluted earnings per share was anti-dilutive.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Accumulated other comprehensive loss</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We include unrealized gains and losses on investments, net of taxes, in accumulated other comprehensive income (loss) along with&#160;adjustments we make to reclassify realized gains and losses on investments from other accumulated comprehensive income (loss) to our condensed consolidated statement of operations. The following table summarizes changes in accumulated other comprehensive income (loss) for the three and nine months ended September 30, 2018 and 2017 (in thousands):</div>

<div><br>
</div>

<table id="z4c2193c8d9044a6dbcb25b95cfdbcf01" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 90%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Beginning balance accumulated other comprehensive loss</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(32,637</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(30,372</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(31,759</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(30,358</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Unrealized gains (losses) on securities (1)</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">133</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">215</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(834</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">610</div>
</td>
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</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Amounts reclassified from accumulated other comprehensive loss</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(374</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Currency translation adjustment</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(28</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(42</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">61</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(77</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net current period other comprehensive income (loss)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">105</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">173</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(773</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">159</div>
</td>
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</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Ending balance accumulated other comprehensive loss</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(32,532</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(30,199</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(32,532</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(30,199</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>
</table>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z25a8f84ff02b43f8aae6eb40064b6d9f" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 18pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">(1)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">There was no income tax expense or benefit related to elements of other comprehensive income (loss) for the three and nine months ended September 30, 2018 and 2017.</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Convertible debt</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Segment information</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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 drugs to treat patients with rare and serious diseases<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">. 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></div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Stock-based compensation expense</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 nine months ended September 30, 2018 and 2017, we used the following weighted-average assumptions in our Black-Scholes calculations:</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: left; TEXT-INDENT: 36pt">Employee Stock Options:</div>

<table id="zf5fe25e51ffd4f7583b4f4f3af415d4c" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 60%; BORDER-COLLAPSE: collapse" cellspacing="0" cellpadding="0" align="center" border="0">
<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="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</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="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</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="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
</tr>

<tr>
<td style="WIDTH: 70.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Risk-free interest rate</div>
</td>
<td style="WIDTH: 2.71%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">2.3%</div>
</td>
<td style="WIDTH: 2.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 2.65%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">1.8%</div>
</td>
</tr>

<tr>
<td style="WIDTH: 70.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Dividend yield</div>
</td>
<td style="WIDTH: 2.71%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">0.0%</div>
</td>
<td style="WIDTH: 2.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 2.65%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">0.0%</div>
</td>
</tr>

<tr>
<td style="WIDTH: 70.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Volatility</div>
</td>
<td style="WIDTH: 2.71%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">63.1%</div>
</td>
<td style="WIDTH: 2.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 2.65%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">66.1%</div>
</td>
</tr>

<tr>
<td style="WIDTH: 70.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Expected life</div>
</td>
<td style="WIDTH: 2.71%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">4.6 years</div>
</td>
<td style="WIDTH: 2.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 2.65%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">4.5 years</div>
</td>
</tr>
</table>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">16</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: left; TEXT-INDENT: 36pt">Board of Director Stock Options:</div>

<table id="z5820414fcea64d3fa8a7d4bdf492939a" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 60%; BORDER-COLLAPSE: collapse" cellspacing="0" cellpadding="0" align="center" border="0">
<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="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</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="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</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="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
</tr>

<tr>
<td style="WIDTH: 70.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Risk-free interest rate</div>
</td>
<td style="WIDTH: 2.71%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">2.8 %</div>
</td>
<td style="WIDTH: 2.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 2.65%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">2.2 %</div>
</td>
</tr>

<tr>
<td style="WIDTH: 70.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Dividend yield</div>
</td>
<td style="WIDTH: 2.71%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">0.0 %</div>
</td>
<td style="WIDTH: 2.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 2.65%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">0.0 %</div>
</td>
</tr>

<tr>
<td style="WIDTH: 70.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Volatility</div>
</td>
<td style="WIDTH: 2.71%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">61.5 %</div>
</td>
<td style="WIDTH: 2.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 2.65%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">61.2 %</div>
</td>
</tr>

<tr>
<td style="WIDTH: 70.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Expected life</div>
</td>
<td style="WIDTH: 2.71%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">6.6 years</div>
</td>
<td style="WIDTH: 2.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 2.65%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">6.6 years</div>
</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">ESPP:</div>

<table id="z0a7caa0dd146411fa8626f4fa90e019c" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 60%; BORDER-COLLAPSE: collapse" cellspacing="0" cellpadding="0" align="center" border="0">
<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="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</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="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</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="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
</tr>

<tr>
<td style="WIDTH: 70.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Risk-free interest rate</div>
</td>
<td style="WIDTH: 2.71%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">1.8%</div>
</td>
<td style="WIDTH: 2.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 2.65%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">0.8%</div>
</td>
</tr>

<tr>
<td style="WIDTH: 70.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Dividend yield</div>
</td>
<td style="WIDTH: 2.71%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">0.0%</div>
</td>
<td style="WIDTH: 2.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 2.65%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">0.0%</div>
</td>
</tr>

<tr>
<td style="WIDTH: 70.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Volatility</div>
</td>
<td style="WIDTH: 2.71%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">47.3%</div>
</td>
<td style="WIDTH: 2.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 2.65%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">59.9%</div>
</td>
</tr>

<tr>
<td style="WIDTH: 70.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Expected life</div>
</td>
<td style="WIDTH: 2.71%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">6 months</div>
</td>
<td style="WIDTH: 2.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 2.65%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 10.66%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">6 months</div>
</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 and members of our board of directors for the nine months ended September 30, 2018 was $51.83 and $42.88 per share, respectively.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following table summarizes stock-based compensation expense for the three and nine months ended September 30, 2018 and 2017 (in thousands). Our consolidated non-cash stock-based compensation expense includes $12.7 million and $4.7 million of stock-based compensation expense for Akcea for the three months ended September 30, 2018 and 2017, respectively, and $31.2 million and $11.8 million for the nine months ended September 30, 2018 and 2017, respectively.</div>

<div><br>
</div>

<table id="z014cca9ab0094d6199f9376a3c256e39" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom"></td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Research, development and patent</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">18,780</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">16,181</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">57,698</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">48,443</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Selling, general and administrative</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">16,103</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,291</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">39,512</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">15,199</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Total non-cash stock-based compensation expense</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">34,883</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">21,472</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">97,210</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">63,642</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">As of September 30, 2018, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options and RSUs was $139.5 million and $32.6 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 1.3 years and 1.6 years, respectively.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left; TEXT-INDENT: 36pt">Impact of recently issued accounting standards</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In February 2016, the FASB issued amended accounting guidance related to lease accounting, which will require us to record all leases with a term longer than one year on our balance sheet. When we record leases on our balance sheet under the new guidance, we will record a liability with a value equal to the present value of payments we will make over the life of the lease and an asset representing the underlying leased asset. The new accounting guidance requires us to determine if our leases are operating or financing leases. We will record expense for operating leases on a straight-line basis as an operating expense. If we determine a lease is a financing&#160;lease, we will record both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. The new lease standard is effective for annual and interim periods beginning after December 15, 2018, with early adoption permitted. We will adopt this guidance on January 1, 2019. We can choose from two methods of adoption. The first method requires us to reflect our leases on our balance sheet in the earliest comparative period presented in our financial statements. The second method requires us to reflect the impact of adoption on the date we adopt the new guidance and recognize a cumulative-effect adjustment to the opening balance of our accumulated deficit in that period. We are currently determining the method we will use to adopt the new guidance and assessing the effects the new guidance will have on our consolidated financial statements and disclosures.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 consolidated financial statements and disclosures.</div>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">17</font></div>

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</div>
</div>

<div style="TEXT-ALIGN: left"><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In December 2017, the SEC staff issued guidance to address how companies should account for the Tax Act of 2017, or the Tax Act, when an entity does not have the necessary information to complete the accounting for the Tax Act and gives entities up to one year from the enactment of the Tax Act to finalize their amounts. We recognized provisional amounts in our 2017 financial statements and in these financial statements. The ultimate impact may differ materially from these provisional amounts due to, among other things, additional analysis, changes in our interpretations and assumptions, additional regulatory guidance that may be issued, and other actions we may take resulting from the Tax Act. We will assess and update our provisional amounts and disclosures, as necessary, at year end 2018.</div>

<div style="TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In February 2018, the FASB issued updated guidance for reclassification of tax effects from accumulated other comprehensive income (loss). The updated guidance gives entities an option to reclassify amounts included in accumulated other comprehensive income (loss) that under the Tax Act do not have a way to be relieved, and allows a one-time reclassification to retained earnings. The updated guidance is effective for all entities for fiscal years beginning after December 31, 2018, and interim periods within those fiscal years. Early adoption is permitted, and adoption is optional. We are currently assessing the effects this updated guidance could have on our consolidated financial statements and timing of potential adoption.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In June 2018, the FASB issued updated guidance to simplify the accounting for stock-based compensation expense for nonemployees. Specifically, we are now expensing grants to nonemployees in a similar manner as grants to employees and our Board of Directors. Previously, we had to re-value these grants at each reporting period to reflect the current fair value. Under the amended guidance, we value grants to nonemployees when we grant them and we will not adjust their value for future changes. We adopted this guidance in the second quarter of 2018 on a prospective basis. The updated guidance did not have a material impact to our financial results.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 consolidated financial statements and timing of adoption.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 anticipate we will adopt this updated guidance on January 1, 2019 and we do not expect it to have a significant impact on our disclosures.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 0.1pt">3.&#160; Investments</div>

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</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">As of September 30, 2018, 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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following table summarizes the contract maturity of the available-for-sale securities we held as of September 30, 2018:</div>

<div><br>
</div>

<table id="z5a38c7c31b3740fdba0df5c566b01368" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 60%; BORDER-COLLAPSE: collapse" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="WIDTH: 83.04%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 46.8pt; TEXT-INDENT: -9pt">One year or less</div>
</td>
<td style="WIDTH: 16.96%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">80%</div>
</td>
</tr>

<tr>
<td style="WIDTH: 83.04%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 46.8pt; TEXT-INDENT: -9pt">After one year but within two years</div>
</td>
<td style="WIDTH: 16.96%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">15%</div>
</td>
</tr>

<tr>
<td style="WIDTH: 83.04%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 46.8pt; TEXT-INDENT: -9pt">After two years but within three years</div>
</td>
<td style="WIDTH: 16.96%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">5%</div>
</td>
</tr>

<tr>
<td style="WIDTH: 83.04%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 46.8pt; TEXT-INDENT: -9pt">Total</div>
</td>
<td style="WIDTH: 16.96%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">100%</div>
</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">As illustrated above, at September 30, 2018, 95 percent of our available-for-sale securities had a maturity of less than two years.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">At September 30, 2018, we had an ownership interest of less than 20 percent in four private companies and one public company 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 company is Antisense Therapeutics Limited.</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">18</font></div>

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</div>
</div>

<div><br>
</div>

<div><br>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following is a summary of our investments (in thousands):</div>

<div style="TEXT-ALIGN: left"><br>
</div>

<table id="z922880eed19a493597ea0df52c3fb52e" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom"></td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2"></td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Gross Unrealized</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2"></td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">September 30, 2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold">Cost </font>(1)</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Gains</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Losses</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Estimated Fair Value</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Available-for-sale securities:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Corporate debt securities (2)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">841,397</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">23</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,264</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">840,156</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Debt securities issued by U.S. government agencies</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">143,008</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(169</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">142,841</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Debt securities issued by the U.S. Treasury (2)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">154,280</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(89</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">154,191</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Debt securities issued by states of the U.S. and political subdivisions of the states (2)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">49,873</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(330</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">49,543</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 4.5pt; TEXT-INDENT: 13.5pt">Total securities with a maturity of one year or less</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,188,558</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">25</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,852</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,186,731</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Corporate debt securities</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">240,208</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">16</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,420</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">238,804</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Debt securities issued by U.S. government agencies</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">32,435</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(109</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">32,326</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Debt securities issued by the U.S. Treasury</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">9,872</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(10</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">9,862</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">31,666</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(551</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">31,115</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 4.5pt; TEXT-INDENT: 13.5pt">Total securities with a maturity of more than one year</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">314,181</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">16</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2,090</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">312,107</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 4.5pt; TEXT-INDENT: 22.5pt">Total available-for-sale securities</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,502,739</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">41</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(3,942</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,498,838</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<table id="z7089af2e9916488380e009d616d3602c" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom"></td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2"></td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Gross Unrealized</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2"></td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">December 31, 2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold">Cost </font>(1)</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Gains</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Losses</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Estimated Fair Value</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Available-for-sale securities:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Corporate debt securities</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">500,599</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(752</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">499,849</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Debt securities issued by U.S. government agencies</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">83,926</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(212</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">83,714</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Debt securities issued by the U.S. Treasury</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">29,428</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(17</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">29,411</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Debt securities issued by states of the U.S. and political subdivisions of the states (2)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">29,240</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(122</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">29,122</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total securities with a maturity of one year or less</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">643,193</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">6</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,103</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">642,096</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Corporate debt securities</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">148,663</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">8</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,059</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">147,612</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Debt securities issued by U.S. government agencies</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">52,779</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(168</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">52,611</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Debt securities issued by the U.S. Treasury</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,409</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,407</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">65,550</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(740</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">64,810</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total securities with a maturity of more than one year</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">268,401</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">8</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,969</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">266,440</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total available-for-sale securities</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">911,594</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">14</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(3,072</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">908,536</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="TEXT-ALIGN: left">
<table id="zfec4b93b53e647f6b5dc498b9a4b35d5" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 18pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">(1)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: left">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Our available-for-sale securities are held at amortized cost.</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: left">
<table id="z1e66803da0d34ce5b10d47ca4089ab93" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 18pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">(2)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: left">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Includes investments classified as cash equivalents on our condensed consolidated balance sheet.</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following is a summary of our investments we consider to be temporarily impaired at September 30, 2018. 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 id="z11e861d4e1604255bd3363a6dfa50135" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0" border="0">
<tr>
<td style="WIDTH: 30%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="WIDTH: 7px; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Less than 12 Months of</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Temporary Impairment</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">More than 12 Months of</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Temporary Impairment</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Total Temporary</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Impairment</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 30%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;(In thousands)</div>
</td>
<td style="WIDTH: 7px; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Number of</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Investments</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Estimated</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Fair Value</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Unrealized</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Losses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Estimated</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Fair Value</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Unrealized</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Losses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Estimated</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Fair Value</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Unrealized</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Losses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 30%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Corporate debt securities</div>
</td>
<td style="WIDTH: 7px; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">495</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">889,172</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,687</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">83,706</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(997</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">972,878</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2,684</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 30%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Debt securities issued by U.S. government agencies</div>
</td>
<td style="WIDTH: 7px; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">51</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">132,231</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(139</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">26,862</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(139</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">159,093</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(278</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 30%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Debt securities issued by the U.S. Treasury</div>
</td>
<td style="WIDTH: 7px; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">32</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">164,053</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(99</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">164,053</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(99</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 30%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
</td>
<td style="WIDTH: 7px; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">48</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">25,687</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(191</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">51,747</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(690</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">77,434</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(881</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 30%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total temporarily impaired securities</div>
</td>
<td style="WIDTH: 7px; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">626</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,211,143</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2,116</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">162,315</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,826</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,373,458</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 7%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(3,942</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">4.&#160; Fair Value Measurements</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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. During the nine months ended September 30, 2018, there were no transfers between our Level 1 and Level 2 investments. When we recognize transfers between levels of the fair value hierarchy, we recognize the transfer on the date the event or change in circumstances that caused the transfer occurs.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following tables present the major security types we held at September 30, 2018 and December 31, 2017 that are regularly measured and carried at fair value. At September 30, 2018 and December 31, 2017, we did not have any financial instruments that we valued using Level 3 inputs. 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):</div>

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<table id="z2a06ad1766704ef9be74f0c12c0397a7" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">At</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30, 2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Quoted Prices in</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Active Markets</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(Level 1)</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Significant Other</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Observable Inputs</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(Level 2)</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Cash equivalents (1)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">395,649</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">395,649</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Corporate debt securities (2)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,078,960</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,078,960</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Debt securities issued by U.S. government agencies (3)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">175,167</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">175,167</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Debt securities issued by the U.S. Treasury (3)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">164,053</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">164,053</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Debt securities issued by states of the U.S. and political subdivisions of the states (3)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">80,658</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">80,658</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,894,487</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">559,702</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,334,785</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<table id="z38fd781483cf4f03b1a36f56176e6c99" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">At</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">December 31, 2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Quoted Prices in</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Active Markets</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(Level 1)</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Significant Other</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Observable Inputs</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">(Level 2)</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Cash equivalents (1)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">86,262</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">86,262</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Corporate debt securities (3)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">647,461</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">647,461</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Debt securities issued by U.S. government agencies (3)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">136,325</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">136,325</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Debt securities issued by the U.S. Treasury (3)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">30,818</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">30,818</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Debt securities issued by states of the U.S. and political subdivisions of the states (4)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">93,932</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">93,932</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr style="HEIGHT: 16px">
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">994,798</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">117,080</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">877,718</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="zea5cfc2b5808477e8c76cda17dd4373e" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 18pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">(1)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Included in cash and cash equivalents on our condensed consolidated balance sheet.</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z5d8cda365d874627805ea971609a117f" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 18pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">(2)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">At September 30, 2018, $19.7 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.</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="zeda7acaf515b4b2f9b00ff2127387f8a" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 18pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">(3)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Included in short-term investments on our condensed consolidated balance sheet.</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z8f1d2cb032934912aab47ea1fd53ce0e" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 18pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">(4)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">At December 31, 2017, $3.5 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.</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Other Fair Value Disclosures</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Novartis Future Stock Purchase</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In January 2017, we and Akcea entered into a SPA with Novartis. As part of the SPA, Novartis was required to purchase $50 million of Akcea&#8217;s common stock at the IPO price or our common stock at a premium if an IPO did not occur by April 2018. Therefore, at the inception of the SPA, we recorded a $5.0 million asset representing the fair value of the potential future premium we could have received if Novartis purchased our common stock. We determined the fair value of the future premium by calculating the value based on the stated premium in the SPA and estimating the probability of an Akcea IPO. We also included a <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">lack of marketability discount when we determined the fair value of the premium because we would have issued unregistered shares to Novartis if they had purchased our common stock. We measured this asset using Level 3 inputs and recorded it in other assets on our consolidated balance sheet. Because Akcea completed its IPO before April 2018, Novartis did not purchase additional shares of Ionis stock. Therefore, we wrote-off the remaining balance to other expenses in the third quarter of 2017 because this asset no longer had any value.</font></div>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">20</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following is a reconciliation of the potential premium we would have received if Akcea had not completed its IPO, measured at fair value on a recurring basis using significant unobservable inputs (Level 3) for the nine months ended September 30, 2017 (in thousands):</div>

<table id="zf6b8b3073a1d408db14c6e4fa33b953f" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 70%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 88%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Beginning balance of Level 3 instruments at January 1, 2017</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 88%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Value of the potential premium we would have received from Novartis at inception of the SPA (January 2017)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,035</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 88%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Recurring fair value adjustment during the nine months ended September 30, 2017</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(5,035</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 88%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Ending balance of Level 3 instruments at September 30, 2017</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our 1 percent notes had a fair value of $725.7 million at September 30, 2018. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">5.&#160; Other Obligations</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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, we can borrow up to a maximum of $30 million of revolving credit for general working capital purposes. Under the credit agreement interest is payable monthly in arrears on the outstanding principal at a borrowing rate based on our option of:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">a floating rate equal to the one-month London Interbank Offered Rate, or LIBOR, in effect plus 1.25 percent per annum;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">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</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">a fixed rate equal to the LIBOR swap rate during the period of the loan.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Additionally, we pay 0.25 percent per annum, payable quarterly in arrears, for any amount unused under the credit facility. As of September 30, 2018 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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The credit agreement includes customary affirmative and negative covenants and restrictions. We are in compliance with all covenants of the credit agreement.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Research and Development and Manufacturing Facilities</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">In July 2017, </font>we purchased the building that houses our primary R&amp;D facility and the building that houses our manufacturing facility for $79.4 million and $14.0 million, respectively. We financed the purchase of our primary R&amp;D facility and our 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 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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">6.&#160; Collaborative Arrangements and Licensing Agreements</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Below, we have included all of our significant collaborations because we adopted Topic 606 on January 1, 2018. We have included new disclosures for each of our collaborations as required under Topic 606.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Strategic Partnership</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Biogen</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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 drugs with Biogen's expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved drug to treat people with spinal muscular atrophy, or SMA. In</font> December 2017, we entered into a collaboration with Biogen to identify <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">new antisense drugs for the treatment of SMA</font>. <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Additionally, we and Biogen are currently developing six other drugs to treat neurodegenerative diseases under these collaborations, including IONIS-SOD1</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> for ALS, IONIS-MAPT</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx </sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">for Alzheimer&#8217;s disease</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">,</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> IONIS-C9</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx </sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">for ALS, and IONIS-BIIB6</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">, IONIS-BIIB7</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> and IONIS-BIIB8</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> to treat undisclosed neurodegenerative diseases. In addition to these drugs, we and Biogen are evaluating numerous additional targets to develop drugs to treat neurological diseases. Most recently, in April 2018, we entered into a new strategic collaboration for the treatment of neurological diseases with Biogen. From inception through September 2018, we have received over $1.9 billion from our Biogen collaborations, including $1 billion we received from Biogen in the second quarter of 2018 when we entered into the 2018 strategic neurology collaboration.</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In January 2012, we entered into a collaboration agreement with Biogen to develop and commercialize SPINRAZA, an RNA-targeted therapy for the treatment of SMA. In December 2016, the FDA approved SPINRAZA for the treatment of SMA in pediatric and adult patients.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">From inception through September 2018, we earned $717 million in total revenue under our SPINRAZA collaboration, including $281 million in revenue from SPINRAZA royalties and $436 million in R&amp;D revenue. We are receiving tiered royalties ranging from 11 percent to 15 percent on any sales of SPINRAZA. We have exclusively in-licensed patents related to SPINRAZA from Cold Spring Harbor Laboratory and the University of Massachusetts. We pay Cold Spring Harbor Laboratory and the University of Massachusetts a low single digit royalty on sales of SPINRAZA. Biogen is responsible for all further global development, regulatory and commercialization activities and costs for SPINRAZA.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Over the course of our SPINRAZA collaboration, we identified two performance obligations, which were to perform R&amp;D services and to deliver the SPINRAZA license to Biogen. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. We recognized revenue for our R&amp;D services performance obligation over our period of performance through December 2016. We recognized the $75 million license fee for SPINRAZA as revenue when we delivered the license to Biogen in July 2016 because Biogen 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 Biogen.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We also earned additional milestone payments subsequent to delivering the license to Biogen that we recognized in full in the period each milestone payment became probable because we did not have a performance obligation related to each milestone payment. For example, we received $90 million of milestone payments for the approval of SPINRAZA in the EU and Japan in 2017 and recognized the full amounts into revenue in the period Biogen achieved the milestone events.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Neurology</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In December&#160;2012, we and Biogen entered into a collaboration agreement to develop and commercialize novel antisense drugs to up to three targets to treat neurodegenerative diseases. We are responsible for the development of each of the drugs through the completion of the initial Phase 2 clinical study for such drug. Biogen has the option to license a drug from each of the three programs through the completion of the first Phase 2 study for each program. We are currently advancing IONIS-MAPT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> for Alzheimer&#8217;s disease under this collaboration. If Biogen exercises its option for a drug, it will assume all further global development, regulatory and commercialization responsibilities and costs for that drug.&#160;</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Under the terms of the agreement, we received an upfront payment of $30 million. Over the term of the collaboration, we are eligible to receive up to $210 million in a license fee and milestone payments per program, plus a mark-up on the cost estimate of the Phase 1 and 2 studies. The $210 million per program consists of up to $10 million in development milestone payments, plus a mark-up on the cost estimate of the Phase 1 and 2 studies and up to $130 million in milestone payments if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on sales of any drugs resulting from each of the three programs. From inception through September 2018, we have received $58 million in milestone payments and upfront fees under this collaboration. We will achieve the next payment of $7.5 </font>million if we continue to advance IONIS-MAPT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for Biogen. At inception, we determined the transaction price to be the $30 million upfront payment we received and allocated it to our single performance obligation. As we achieve milestone payments for our R&amp;D services, we include these amounts in our transaction price for our R&amp;D services performance obligation. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> currently estimate we will satisfy our performance obligation in </font>December 2020. From inception through <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">September 2018</font>, we have included $40 million in total payments in the transaction price for our R&amp;D services performance obligation.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: left; TEXT-INDENT: 36pt">2013 Strategic Neurology</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In September&#160;2013, we and Biogen entered into a long-term strategic relationship focused on applying antisense technology to advance the treatment of neurodegenerative diseases. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for neurological diseases and has the option to license drugs resulting from this collaboration. The exclusivity for neurological diseases will last through September 2019, and may be extended for any drug development programs Biogen is pursuing under the collaboration. We will usually be responsible for drug discovery and early development of antisense drugs and Biogen will have the option to license antisense drugs after Phase 2 proof of concept. In October 2016, we expanded our collaboration to include additional research activities we will perform. If Biogen exercises its option for a drug, it will assume all further global development, regulatory and commercialization responsibilities and costs for that drug. We are currently advancing five drugs, IONIS-SOD1<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>, IONIS-C9<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>, IONIS-BIIB6<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>, IONIS-BIIB7<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> and IONIS-BIIB8<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> under this collaboration. Biogen will be responsible for all of the drug discovery and development activities for drugs using other modalities.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Under the terms of the agreement, we received an upfront payment of $100 million and are eligible to receive milestone payments, license fees and royalty payments for all drugs developed through this collaboration, with the specific amounts dependent upon the modality of the molecule advanced by Biogen. For each antisense molecule that is chosen for drug discovery and development under this collaboration, we are eligible to receive up to approximately $260 million in a license fee and milestone payments per program. The $260 million per program consists of approximately $60 million in development milestones, including amounts related to the cost of clinical trials, and up to $130 million in milestone payments if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on sales from any antisense drugs developed under this collaboration. If Biogen chooses to advance drugs using other modalities, such as small molecules or monoclonal antibodies, we are eligible to receive up to $90 million in milestone payments per program. The $90 million per program consists of up to $35 million in development milestone payments and up to $55 million in milestone payments if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered single-digit royalties on sales from any drugs using non-antisense modalities developed under this collaboration. From inception through September 2018, we have received over $170 million in upfront fees, milestone payments and other payments under this collaboration, not including a $10 million milestone payment we earned in the third quarter of 2018 for Biogen&#8217;s initiation of a Phase 1 study for IONIS-C9<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx </sub>which we received in the fourth quarter of 2018. We will achieve the next payment of up to $10 million if we advance a program under this collaboration.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">At the commencement of our strategic neurology collaboration, we identified one performance obligation, which was to perform R&amp;D services for Biogen. At inception, we determined the transaction price to be the $100 million upfront payment we received and allocated it to our single performance obligation. As we achieve milestone payments for our R&amp;D services, we include these amounts in our transaction price for our R&amp;D services performance obligation. We are recognizing revenue for our R&amp;D services performance obligation based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">. </font>We<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> currently estimate we will satisfy our performance obligation in</font> September 2019. From inception through <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">September 2018</font>, we have included $145 million in total payments in the transaction price for our R&amp;D services performance obligation. <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">In the third quarter of 2018, we earned a $10 million milestone payment when Biogen initiated a Phase 1 study of IONIS-C9</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">. We recognized this milestone payment in full in the third quarter because we do not have any performance obligations related to this milestone payment. Additionally, we concluded that the payment is not related to our R&amp;D services performance obligation.</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">New antisense drugs for the treatment of SMA</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">In December 2017, we entered into a collaboration agreement with Biogen to </font>identify <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">new antisense drugs for the treatment of SMA</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">. </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Biogen will have the option to license therapies arising out of this collaboration following the completion of preclinical studies. Upon licensing, Biogen </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">will be responsible for all further global development, regulatory and commercialization activities and costs for such therapies</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">. Under the collaboration agreement, we received a&#160;</font>$25 million<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#160;upfront payment in December 2017. We will receive development and regulatory milestone payments from Biogen if new drugs advance towards marketing approval. </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">In total over the term of our collaboration, we are eligible to receive up to $1.2 billion in license fees, milestone payments and other payments, including up to $80 million for the achievement of development milestones, up to $180 million for the achievement of commercialization milestones and up to $800 million for the achievement of sales milestones. In addition, we are eligible to receive tiered royalties </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">from the mid-teens to </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">mid-20 percent range </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">on net sales.</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> We will achieve the next payment of up to $60 million</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">for the license of a drug under this collaboration. </font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for Biogen. We determined the transaction price to be the $25 million upfront payment we received when we entered into the collaboration. We allocated the transaction price to our single performance obligation. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> currently estimate we will satisfy our performance obligation in</font> December 2020.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: left; TEXT-INDENT: 36pt">2018 Strategic Neurology Collaboration</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In April 2018, we and Biogen entered into a new strategic collaboration to develop novel antisense drugs for a broad range of neurological diseases and entered into a SPA. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for these diseases for 10 years. We are responsible for the identification of antisense drug candidates based on selected targets, while Biogen will have the option to license therapies arising out of this collaboration and will be responsible for and pay for non-clinical studies, clinical development, manufacturing, and commercialization.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">In the second quarter of 2018, we received </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$1 billion from Biogen, comprised of $</font>625<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> million to purchase our stock at a 25 percent cash premium and $</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">375</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> million in an upfront payment. </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We are eligible to receive up to $</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #222222">270</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> million for each drug that achieves marketing approval. </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">In addition, we are eligible to receive tiered royalties </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">up to the 20 percent</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> range </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">on net sales.</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> We will achieve the next payment of $7.5 million if Biogen designates a target</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> under this collaboration. </font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">At the commencement of this collaboration, </font>we identified one performance obligation, which was to perform R&amp;D services for Biogen.<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> We determined our transaction price to be $552 million, comprised of $375 million from the upfront payment and $177 million for the premium paid by Biogen for its purchase of our common stock.</font> We determined the fair value of the premium we received by using the stated premium in the SPA and applying a lack of marketability discount. We included a lack of marketability discount in our valuation of the premium because Biogen <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">received restricted shares</font>. We allocated the transaction price to our single performance obligation. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> currently estimate we will satisfy our performance obligation in </font>June 2028.</div>

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<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">23</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>

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<table id="z5b2ff933a08e49cba59e0b8d646c9a0b" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 70%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
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<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
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<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
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<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
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<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
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<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -27pt">SPINRAZA royalties (commercial revenue)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">70.0</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">32.9</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">167.7</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">60.5</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
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<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">R&amp;D revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">34.8</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">54.9</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">66.9</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">137.1</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -9pt">Total revenue from our relationship with Biogen</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">104.8</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">87.8</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">234.6</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">197.6</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -9pt">Percentage of total revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">72</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">74</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">58</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">57</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
</tr>
</table>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our condensed consolidated balance sheet at September 30, 2018 and <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">December 31, 2017 </font>included deferred revenue of $593.6 million and $93.6 million, respectively, related to our relationship with Biogen.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Research, Development and Commercialization Partners</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">AstraZeneca</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Cardiac, Renal and Metabolic Diseases Collaboration</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">In July 2015, we and AstraZeneca formed a collaboration to discover and develop antisense therapies for treating cardiac, renal and metabolic diseases. Under our collaboration AstraZeneca has licensed three drugs from us. As part of the agreement, we granted AstraZeneca an exclusive license to IONIS-AZ4-2.5-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">, a drug we designed to treat cardiovascular disease and our first </font>drug that combines our Generation 2.5 and<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> LIgand-Conjugated Antisense, or LICA, technology. We also granted AstraZeneca the option to license a drug for each additional target advanced under this research collaboration. In February 2018, AstraZeneca licensed a second drug under our collaboration, IONIS-AZ5-2.5</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">, a drug we designed to </font>treat a genetically associated form of kidney disease<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">. In March 2018, AstraZeneca licensed a third drug under our collaboration, IONIS-AZ6-2.5-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">, a drug we designed to </font>inhibit an undisclosed target to treat patients with nonalcoholic steatohepatitis, or NASH<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">. AstraZeneca is responsible for all further global development, regulatory and commercialization activities and costs for IONIS-AZ4-2.5-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">, IONIS-AZ5-2.5</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> and</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">&#160;</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">IONIS-AZ6-2.5-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> and any other future drugs AstraZeneca licenses.</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Under the terms of the agreement, we received a $65 million upfront payment. We are eligible to receive license fees and milestone payments of up to more than $4 billion as drugs under this collaboration advance, including up to $1.1 billion for the achievement of development milestones and up to $2.9 billion for regulatory milestones. In addition, we are eligible to receive tiered royalties up to the low teens on sales from any product that AstraZeneca successfully commercializes under this collaboration agreement. From inception through September 2018, we have received over $165 million in upfront fees, license fees, milestone payments, and other payments under this collaboration, including a $10 million milestone payment we earned in the third quarter of 2018 when AstraZeneca initiated a Phase 1 trial for IONIS-AZ4-2.5-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>. We will achieve the next payment of $10 million under this collaboration if we advance a drug under this collaboration<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">.</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for AstraZeneca. We determined the transaction price to be the $65 million upfront payment we received and we allocated it to our single performance obligation. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy this performance obligation relative to our total effort expected to satisfy our performance obligation. We<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> currently estimate we will satisfy this performance obligation in</font> August 2021. As we achieve milestone payments for our R&amp;D services, we include these amounts in our transaction price for our R&amp;D services performance obligation. From inception through <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">September 2018</font>, we have included $90 million in payments in the transaction price for our R&amp;D services performance obligation.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We identified separate performance obligations upon AstraZeneca&#8217;s license of IONIS-AZ5-2.5<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> and IONIS-AZ6-2.5-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> in the first quarter of 2018 because the licenses are distinct from our other performance obligation and each other. We recognized each $30 million license fee in the first quarter of 2018 because AstraZeneca had full use of the licenses without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the licenses after we delivered them to AstraZeneca.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In the third quarter of 2018, we earned a $10 million milestone payment when AstraZeneca initiated a Phase 1 study of IONIS-AZ4-2.5-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>. We recognized this milestone payment in full in the third quarter because we do not have any performance obligations related to this milestone payment. Additionally, we concluded that the payment is not related to our R&amp;D services performance obligation.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Oncology Collaboration</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">In December&#160;2012, we entered into a collaboration agreement with AstraZeneca to discover and develop antisense drugs to treat cancer.&#160;As part of the agreement, we granted AstraZeneca an exclusive license to develop and commercialize </font>danvatirsen (formerly <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">IONIS-STAT3-2.5</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">) for the treatment of cancer. AstraZeneca is now responsible for all global development, regulatory and commercialization activities for </font>danvatirsen<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">. We and AstraZeneca have evaluated </font>danvatirsen<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> in people with head and neck cancer, advanced lymphoma and advanced metastatic hepatocellular carcinoma. AstraZeneca is evaluating </font>danvatirsen<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> in combination with Imfinzi (durvalumab), AstraZeneca&#8217;s programmed death ligand, or PD-L1, blocking drug, in people with head and neck cancer, metastatic bladder cancer and metastatic non-small cell lung cancer. In addition, we and AstraZeneca established an oncology research program. AstraZeneca has the option to license drugs resulting from the program, and if AstraZeneca exercises its option for a drug, it will be responsible for all further global development, regulatory and commercialization activities and costs for such drug.</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Under the terms of this agreement, we received $31 million in upfront payments. We are eligible to receive milestone payments and license fees from AstraZeneca as programs advance in development. If AstraZeneca successfully develops </font>danvatirsen<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> and another drug under the research program, we could receive license fees and milestone payments of up to more than $450 million, including up to $152 million for the achievement of development milestones and up to $275 million for the achievement of regulatory milestones.&#160;In addition, we are eligible to receive tiered royalties up to the low to mid-teens on sales from any drugs resulting from these programs. From inception through September 2018, we have received $97.8 million in upfront fees, milestone payments, and other payments under this oncology collaboration, not including nearly $30 million in milestone payments we achieved when AstraZeneca advanced</font> two programs in the fourth quarter of 2018. We <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">will achieve the next payment of up to $25.0 million </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">if we advance a drug under our cancer research program with AstraZeneca.</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">At the commencement of this collaboration, we identified four performance obligations. We determined the transaction price to be the $31 million in upfront payments we received. We allocated the transaction price based on the estimated stand-alone selling price of each of our performance obligations and recognized the associated revenue over the period of our performance. We recognized revenue for three of our obligations over our period of performance, concluding in March 2014. Our remaining performance obligation was to perform R&amp;D services. We allocated $7.6 million to this performance obligation and recognized the associated revenue over the period of our performance, which ended in February 2018. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with AstraZeneca (in millions, except percentage amounts):</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -27pt">R&amp;D revenue</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">14.2</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">86.5</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">14.8</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Percentage of total revenue</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4</div>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">21</div>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Our </font>condensed consolidated balance sheet at <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">September 30, 2018 and December 31, 2017 included deferred revenue of $44.9 million and $57.7 million, respectively, related to our relationship with AstraZeneca.</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Bayer</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> for the prevention of thrombosis. We were responsible for completing a Phase 2 study of IONIS-FXI<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> in people with end-stage renal disease on hemodialysis. Under the terms of the agreement, we received a $100 million upfront payment in the second quarter of 2015. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> and to initiate development of IONIS-FXI-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>, which Bayer licensed. In conjunction with the decision to advance these programs, we received a $75 million payment from Bayer. We are conducting a Phase 2b study evaluating IONIS-FXI<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> in people with end-stage renal disease on hemodialysis to finalize dose selection. Additionally, we plan to develop IONIS-FXI-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> through Phase 1. Following these studies and Bayer's decision to further advance these programs, Bayer will be responsible for all global development, regulatory and commercialization activities and costs for both drugs.&#160;</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We are eligible to receive additional milestone payments as each drug advances toward the market. In total over the term of this collaboration, we are eligible to receive up to $385 million in license fees, milestone payments and other payments, including up to $125 million for the achievement of development milestones and up to $110 million for the achievement of commercialization milestones. In addition, we are eligible to receive tiered royalties in the low to high 20 percent range on gross margins of both drugs combined. From inception through September 2018, we have received over $175 million from our Bayer collaboration. We will achieve the next payment of $10 million if a program advances under this collaboration.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">At the commencement of this collaboration, we identified three performance obligations. We determined the transaction price to be the $100 million in upfront payment we received. We allocated the transaction price based on the relative stand-alone selling prices of each of our performance obligations and recognized the associated revenue as follows:</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="zac7fa23b841642c9bae7873b853213d9" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">We recognized $91.2 million for the exclusive license of IONIS-FXI<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx </sub>in May 2015 because Bayer <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">had full use of the license without any continuing involvement from us</font>.</div>
</td>
</tr>
</table>
</div>

<div style="TEXT-ALIGN: justify">
<table id="zcd3342eaf72f4af59a1e71306b833949" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">We recognized $4.3 million for the R&amp;D services for IONIS-FXI<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> over the period of our performance, which ended in November 2016.</div>
</td>
</tr>
</table>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z627b9742eb6d4802b4eb02fe14f18505" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">We allocated $4.5 million for API, which we are recognizing into revenue as we deliver the API.</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In February 2017, when we amended our collaboration with Bayer, we identified two new performance obligations<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">, one for the license of IONIS-FXI-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> and one for R&amp;D services</font>. We determined the transaction price to be the $75 million payment. We allocated $64.9 million to <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">the license of IONIS-FXI-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> based on its estimated stand-alone selling price and recognized the associated revenue upon our delivery of the license in the first quarter of 2017. We allocated $10.1 million to our R&amp;D services performance obligation based on an estimated stand-alone selling price. </font>We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> currently estimate we will satisfy our </font>R&amp;D services <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">performance obligation in</font> May 2019.</div>

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<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">25</font></div>

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</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Bayer (in millions, except percentage amounts):</div>

<div><br>
</div>

<table id="z5412e89db8ea45168b34ba636f8d42fa" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 70%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -27pt">R&amp;D revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1.9</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.4</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3.3</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">66.0</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Percentage of total revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">19</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our condensed consolidated balance sheet at September 30, 2018 and <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">December 31, 2017 </font>included deferred revenue of $6.0 million and $9.3 million, respectively, related to our relationship with Bayer.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Janssen Biotech, Inc.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In December&#160;2014, we entered into a collaboration agreement with Janssen Biotech, Inc. to discover and develop antisense drugs that can be locally administered, including oral delivery, to treat autoimmune disorders of the gastrointestinal tract. Janssen has the option to license drugs from us through the designation of a development candidate for up to three programs. Prior to option exercise we are responsible for the discovery activities to identify a development candidate. If Janssen exercises an option for one of the programs, it will be responsible for the global development, regulatory and commercial activities under that program. Under the terms of the agreement, we received $35 million in upfront payments. We are eligible to receive up to more than $800 million in license fees and milestone payments for these programs, including up to $175 million for the achievement of development milestones, up to $440 million for the achievement of regulatory milestones and up to $180 million for the achievement of commercialization milestones. From inception through September 2018, we have received $75 million, including $15 million in license fees when Janssen licensed IONIS-JBI1-2.5<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> and IONIS-JBI2-2.5<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> from us in 2016 and 2017, respectively. We also received $5 million in January 2018 for the initiation of a Phase 1 study of IONIS-JBI1-2.5<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx </sub>in late 2017. In addition, we are eligible to receive tiered royalties up to the near teens on sales from any drugs resulting from this collaboration. We will achieve the next payment of $5 million if Janssen continues to advance a target under this collaboration.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for Janssen. We determined the transaction price to be the $35 million upfront payments we received. We allocated the <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$35 million</font> to our single performance obligation. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. We recognized revenue for our R&amp;D services performance obligation over our period of performance, through November 2017.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We identified separate performance obligations each time Janssen licensed one of our drugs under our collaboration because the licenses we granted to Janssen were distinct from our other performance obligations. We recognized the $10 million license fee for IONIS-JBI1-2.5<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> in July 2016 and $5 million for the license of IONIS-JBI2-2.5<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> in November 2017, because Janssen had full use of the licenses without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the licenses after we delivered them to Janssen.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Janssen (in millions, except percentage amounts):</div>

<div><br>
</div>

<table id="z219e3a1fd45d4a5d8a1985307086d7b4" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 70%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -27pt">R&amp;D revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.9</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3.4</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">6.6</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">18.1</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Percentage of total revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We did not have any deferred revenue from our relationship with Janssen at September 30, 2018 or December 31, 2017.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Roche</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: left; MARGIN-LEFT: 36pt">Huntington's Disease</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In April&#160;2013, we formed an alliance with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, to develop treatments for Huntington's disease, or HD, based on our antisense technology. Roche had the option to license the drugs from us through the completion of the first Phase 1 trial. Under the agreement, we are responsible for the discovery and development of an antisense drug targeting huntingtin, or HTT, protein. We evaluated a drug targeting HTT, IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>, in a Phase 1/2a clinical study in people with early stage HD.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In December 2017, upon completion of the Phase 1/2a study, Roche exercised its option to license IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx </sub>and is now responsible for the global development, regulatory and commercialization activities for IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>. Under the terms of the agreement, we received an upfront payment of $30 million in April&#160;2013.&#160;In December 2016, we updated development activities for IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> and as a result we were eligible for an additional $3 million payment, which we achieved in 2017. We are eligible to receive up to $365 million in a license fee and milestone payments including up to $70 million for the achievement of development milestones, up to $170 million for the achievement of regulatory milestones and up to $80 million for the achievement of commercialization milestones. In addition, we are eligible to receive up to $136.5 million in milestone payments for each additional drug successfully developed.&#160;We are also eligible to receive tiered royalties up to the mid-teens on any sales of any product resulting from this alliance. From inception through September 2018, we have received over $110 million in upfront fees, milestone payments and license fees for advancing IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>, including the $45 million license fee we received in January 2018 for IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>. We will achieve the next payment of $35 million if Roche initiates a pivotal study for IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>.</div>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">26</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for Roche. We determined the transaction price to be the $30 million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. We recognized revenue for our R&amp;D services performance obligation over our period of performance, through September 2017.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We identified a second performance obligation upon Roche&#8217;s license of IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> in the fourth quarter of 2017 because the license we granted to Roche is distinct from our other performance obligation. We recognized the $45 million license fee for IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> as revenue at that time because Roche had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Roche.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We do not have any remaining performance obligations related to IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> under this collaboration with Roche, however we can still earn additional payments and royalties as Roche advances IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">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"> for Complement-Mediated Diseases</font></div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">In October 2018, we entered into a collaboration agreement with Roche to</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> develop IONIS-FB-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#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 are exploring the drug in a severe and rare renal indication.&#160;</font>Roche<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#160;has the option to license IONIS-FB-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#160;at the completion of these studies. Upon licensing,&#160;</font>Roche <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">will be responsible for all further global development, regulatory and commercialization activities and costs.</font></div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Under this new collaboration agreement, we received a&#160;</font>$75 million<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#160;upfront payment in October 2018. We are eligible to receive up to&#160;</font>$684 million<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#160;in development, regulatory and sales milestone payments and license fees. In addition, we are also eligible to receive tiered royalties from the high teens to twenty percent on net sales. We will achieve the next payment of $20 million when we advance </font>the Phase 2 study in patients with dry AMD<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">.</font></div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):</div>

<div><br>
</div>

<table id="z2ea1f4bfe1354042bdd4c65866b1e7fe" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 70%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -27pt">R&amp;D revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1.8</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4.5</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5.4</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5.9</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Percentage of total revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We did not have any deferred revenue from our relationship with Roche at September 30, 2018 or December 31, 2017.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">GSK</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In March&#160;2010, we entered into an alliance with GSK using our antisense drug discovery platform to discover and develop new drugs against targets for rare and serious diseases, including infectious diseases and some conditions causing blindness. Under the terms of the agreement, we received upfront payments of $35 million.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">GSK is advancing two drugs targeting hepatitis B virus, or HBV, under our collaboration: IONIS-HBV<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>&#160;and IONIS-HBV-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>. GSK is currently conducting Phase 2 studies for both of these drugs, which we designed to reduce the production of viral proteins associated with HBV infection. In March 2016, we and GSK amended the development plan for IONIS-HBV<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> to allow GSK to conduct all further development activities for this program. GSK has the exclusive option to license the drugs resulting from this alliance at Phase 2 proof-of-concept for a license fee.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Under our agreement, if GSK successfully develops these drugs and achieves pre-agreed sales targets, we could receive license fees and milestone payments of $262 million, including up to $47.5 million for the achievement of development milestones, up to $120 million for the achievement of regulatory milestones and up to $70 million for the achievement of commercialization milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on sales from any product that GSK successfully commercializes under this alliance. From inception through September 2018, we have received more than $162 million in payments under this alliance with GSK. We will achieve the next payment of up to $25 million if GSK licenses a drug under this program.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for GSK. We determined the transaction price to be the $35 million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. We recognized revenue for our R&amp;D services performance obligation over our period of performance, through March 2015. We do not have any remaining performance obligations under our collaboration with GSK, however we can still earn additional payments and royalties as GSK advances these drugs.</div>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">27</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):</div>

<div><br>
</div>

<table id="z9ddb05673b9841c4bf36d6269866b066" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 70%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -27pt">R&amp;D revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.1</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4.6</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1.5</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">14.4</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Percentage of total revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our revenue for the nine months ended September 30, 2017, was from our work on the programs under our collaboration with GSK. We did not have any deferred revenue from our relationship with GSK at September 30, 2018 or December 31, 2017.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Akcea Collaborations</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following collaboration agreements relate to Akcea, our majority owned affiliate. Our consolidated results include all the revenue earned and cash received under these collaboration agreements. 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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Novartis</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In January 2017, we and Akcea initiated a collaboration with Novartis to develop and commercialize AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> and AKCEA-APOCIII-L<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>Under the collaboration agreement, Novartis has an exclusive option to further develop and commercialize AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> and AKCEA-APOCIII-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>. 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 drug. If Novartis exercises an option for one of these drugs, Novartis will be responsible for all further global development, regulatory and co-commercialization activities and costs for such drug.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Akcea received a $75 million upfront payment in the first quarter of 2017, of which it retained $60 million and paid us $15 million as a sublicense fee. If Novartis exercises its option for a drug, Novartis will pay Akcea a license fee equal to $150 million for each drug it licenses. In addition, for AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>, Akcea is eligible to receive up to $600 million in milestone payments, including $25 million for the achievement of a development milestone, up to $290 million for the achievement of regulatory milestones and up to $285 million for the achievement of commercialization milestones. In addition, for AKCEA-APOCIII-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>, Akcea is eligible to receive up to $530 million in milestone payments, including $25 million for the achievement of a development milestone, up to $240 million for the achievement of regulatory milestones and up to $265 million for the achievement of commercialization milestones. Akcea is also eligible to receive tiered royalties in the mid-teens to low 20 percent range on net sales of AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> and AKCEA-APOCIII-L<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; COLOR: #000000">Novartis will reduce these royalties upon the expiration of certain patents or if a generic competitor negatively impacts the product in a specific country. </font>Akcea will pay 50 percent of these license fees, milestone payments and royalties to us as a sublicense fee.<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> Akcea plans to co-commercialize any licensed drug commercialized by Novartis in selected markets under terms and conditions that we plan to negotiate with Novartis in the future, through its specialized sales force.</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In conjunction with this collaboration, we and Akcea entered into a SPA with Novartis. As part of the SPA, Novartis purchased 1.6 million shares of our common stock for $100 million in the first quarter of 2017. As part of the SPA, Novartis was required to purchase $50 million of Akcea&#8217;s common stock at the IPO price or our common stock at a premium if an IPO did not occur by April 2018. Under the SPA, in July 2017, Novartis purchased $50 million of Akcea&#8217;s common stock in a separate private placement concurrent with the completion of its IPO at a price per share equal to the IPO price.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">At the commencement of this collaboration, we identified four separate performance obligations:</div>

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<div style="TEXT-ALIGN: justify">
<table id="zfa52cc01c9bb4249abf29a71e2b6718d" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">R&amp;D services for AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>;</div>
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<div style="TEXT-ALIGN: justify">
<table id="z765648b5d38342129d08db1f4059e638" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">R&amp;D services for AKCEA-APOCIII-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>;</div>
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<div style="TEXT-ALIGN: justify">
<table id="z4cff8fdcf21141e58dccaad43e48d480" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">API for AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>; and</div>
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<div style="TEXT-ALIGN: justify">
<table id="zf4014e056e784f1ba40e4e3c4a532702" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">API for AKCEA-APOCIII-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>.</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We determined that the R&amp;D services for each drug and the API for each drug were distinct from our other performance obligations.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We determined our transaction price to be $108.4 million, comprised of the following:</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z572ea72a874d495090c2beb227f15135" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$75 million from the upfront payment;</div>
</td>
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</div>

<div style="TEXT-ALIGN: justify">
<table id="z03a9967eb9a64311baaa13c0aa5cd741" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$28.4 million for the premium paid by Novartis for its purchase of our common stock at a premium in the first quarter of 2017; and</div>
</td>
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</table>
</div>

<div style="TEXT-ALIGN: justify">
<table id="zaa4c9ecd425d4307ba423a6a87b44796" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$5.0 million for the potential premium Novartis would have paid if they purchased our common stock in the future.</div>
</td>
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</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We allocated the transaction price based on the estimated stand-alone selling price of each performance obligation as follows:</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="zee7c8d49025248ebb6e2dccb91f31f75" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$64.0 million for the R&amp;D services for <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">AKCEA-APO(a)-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;FONT-FAMILY: 'Times New Roman'">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">;</font></div>
</td>
</tr>
</table>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z70fd758c75e749c4b12cb3202c6d8d9f" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$40.1 million for the R&amp;D services for <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">AKCEA-APOCIII-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;FONT-FAMILY: 'Times New Roman'">Rx</sub>; </div>
</td>
</tr>
</table>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z3adf416a89e146a0a29d6e3ec8b505b8" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">$1.5</font> million for the delivery of AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> API; and</div>
</td>
</tr>
</table>
</div>

<div style="TEXT-ALIGN: justify">
<table id="ze5f809870fda4ff8b5373544f282679d" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">$2.8</font> million for the delivery of AKCEA-APOCIII-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> API.</div>
</td>
</tr>
</table>
</div>

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<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">28</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We are recognizing revenue related to the R&amp;D services for the AKCEA-APO(a)-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> and AKCEA-APOCIII-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> performance obligations as we perform services </font>based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">. </font>We<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> currently estimate we will satisfy the significant portion of our performance obligation for AKCEA-APO(a)-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> by December 2018 with the remainder by the end of March 2019. </font>We<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> currently estimate we will satisfy the significant portion of our performance obligation for AKCEA-APOCIII-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> by June 2019 with the remainder by the end of December 2019. We recognized the amount attributed to the API supply for AKCEA-APO(a)-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> when we delivered it to Novartis in 2017. We recognized the amount attributed to the API supply for AKCEA-APOCIII-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> when we delivered it to Novartis in May 2018.</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 consolidated balance sheet.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):</div>

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</div>

<table id="z9c278c300d1c4c33a04c9e7ef355a5b1" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 70%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -27pt">R&amp;D revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">7.2</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">9.9</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">42.7</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">21.7</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Percentage of total revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">8</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">6</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our condensed consolidated balance sheet at September 30, 2018 and December 31, 2017 included deferred revenue of $34.8 million and $70.7 million, respectively, related to our relationship with Novartis.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">PTC Therapeutics</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In August 2018, Akcea entered into an exclusive license agreement with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America. Under the license agreement, Akcea will receive up to $26 million of payments, including $12 million which it received in the third quarter of 2018, $6 million upon the earlier of FDA or EMA approval of WAYLIVRA and up to $8 million of regulatory milestone payments. Akcea will receive royalties from PTC in the mid-20 percent range on net sales in Latin America for each drug.&#160;PTC's obligation to pay Akcea royalties begins on the earlier of 12 months after the first commercial sale of a product in&#160;Brazil&#160;or the date that PTC recognizes revenue of at least&#160;$10 million&#160;in Latin America. These royalties may be reduced upon expiration of certain patents or if a generic competitor negatively impacts PTC&#8217;s market share. Consistent with the agreements between Ionis and Akcea, the companies will share all payments, including royalties.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">At the commencement of this collaboration, we identified two performance obligations, which were the licenses Akcea granted to PTC to commercialize TEGSEDI and WAYLIVRA in Latin America in the third quarter of 2018. Akcea recognized $12 million in license fee revenue at that time because PTC had full use of both licenses without any continuing involvement from Akcea. Akcea does not have any remaining performance obligations under its collaboration with PTC. Akcea can still earn additional payments and royalties as PTC commercializes the drugs.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Akcea is responsible for the 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 SG&amp;A expense. For example, during the third quarter of 2018, we recognized $7.2 million of sublicense revenue in our Ionis Core operating segment results related to our portion of the PTC license fee Akcea paid us. In our consolidated results, we eliminate this sublicense revenue and expense. Any cash Akcea receives is included in our consolidated balance sheet.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with PTC (in millions, except percentage amounts):</div>

<div><br>
</div>

<table id="zfeaaddb0d85745a8865167f4d8a43294" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 70%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -27pt">R&amp;D revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12.0</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.0</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12.0</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.0</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Percentage of total revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">8</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">%</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our condensed consolidated balance sheet at September 30, 2018 and December 31, 2017 did not include any deferred revenue related to our relationship with PTC.</div>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">29</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">7.&#160; Segment Information and Concentration of Business Risk</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We have two reportable segments Ionis Core and Akcea Therapeutics. </font>At September 30, 2018 we owned approximately 75 percent of Akcea.<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#160;</font>In October 2018, we received an additional 1.7 million shares of Akcea&#8217;s stock when TEGSEDI was approved by the FDA, increasing our ownership percentage to 76 percent. <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Segment income (loss) from operations includes revenue less operating expenses attributable to each segment.</font></div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 drugs for us and our partners. Our Ionis Core segment generates revenue from a multifaceted partnering strategy.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Akcea is </font>a biopharmaceutical company focused on developing and commercializing drugs to treat patients with rare and serious diseases<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">.</font></div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following tables show our segment revenue and income (loss) from operations for the three and nine months ended September 30, 2018 and 2017 (in thousands), respectively.</div>

<div><br>
</div>

<table id="zc62790ed35a340a4bba485dbfa75d883" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">Three Months Ended September 30, 2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Ionis Core</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Akcea Therapeutics</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Elimination of</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Intercompany Activity</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Total</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: top" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: top" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 7.2pt">Commercial revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 25.2pt">SPINRAZA royalties</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">70,010</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">70,010</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 25.2pt">Licensing and other royalty revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">7,946</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12,000</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,200</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12,746</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 43.2pt">Total commercial revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">77,956</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12,000</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,200</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">82,756</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 7.2pt">R&amp;D revenue under collaborative agreements</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">100,105</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">7,241</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(44,707</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">62,639</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 25.2pt">Total segment revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">178,061</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">19,241</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(51,907</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">145,395</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Total operating expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">87,664</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">84,249</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,946</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">163,967</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Income (loss) from operations</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">90,397</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(65,008</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(43,961</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(18,572</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>
</table>

<div><br>
</div>

<table id="z8427304030df41ba9010bfecf33e65ec" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">Three Months Ended September 30, 2017 (as revised)</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Ionis Core</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Akcea Therapeutics</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Elimination of</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Intercompany Activity</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Total</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">Revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: top" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 7.2pt">Commercial revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 25.2pt">SPINRAZA royalties</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">32,890</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">32,890</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 25.2pt">Licensing and other royalty revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,727</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,727</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 43.2pt">Total commercial revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">34,617</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">34,617</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 7.2pt">R&amp;D revenue under collaborative agreements</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">73,791</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">9,906</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">83,697</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 25.2pt">Total segment revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">108,408</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">9,906</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">118,314</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Total operating expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">81,019</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">26,013</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(30</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">107,002</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Income (loss) from operations</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">27,389</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(16,107</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">30</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,312</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<table id="z4ce38eb6cbca4d9496543c1e5a8aad6a" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">Nine Months Ended September 30, 2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Ionis Core</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Akcea Therapeutics</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Elimination of</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Intercompany Activity</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Total</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: top" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: top" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 7.2pt">Commercial revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 25.2pt">SPINRAZA royalties</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">167,743</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">167,743</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 25.2pt">Licensing and other royalty revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">9,432</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12,000</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,200</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">14,232</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 43.2pt">Total commercial revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">177,175</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12,000</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,200</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">181,975</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 7.2pt">R&amp;D revenue under collaborative agreements</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">232,850</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">42,670</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(49,936</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">225,584</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 25.2pt">Total segment revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">410,025</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">54,670</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(57,136</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">407,559</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Total operating expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">279,084</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">213,428</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(12,796</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">479,716</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Income (loss) from operations</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">130,941</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(158,758</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(44,340</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(72,157</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>
</table>

<div><br>
</div>

<table id="zd5409958c9d54b7192929564fea964f5" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">Nine Months Ended September 30, 2017 (as revised)</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Ionis Core</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Akcea Therapeutics</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Elimination of</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Intercompany Activity</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Total</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">Revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: top" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 7.2pt">Commercial revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 25.2pt">SPINRAZA royalties</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">60,467</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">60,467</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 25.2pt">Licensing and other royalty revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,639</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,639</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 43.2pt">Total commercial revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">66,106</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">66,106</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 7.2pt">R&amp;D revenue under collaborative agreements</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">312,976</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">21,712</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(54,407</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">280,281</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 25.2pt">Total segment revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">379,082</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">21,712</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(54,407</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">346,387</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Total operating expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">242,753</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">120,884</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(54,497</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">309,140</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Income (loss) from operations</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">136,329</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(99,172</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">90</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">37,247</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">30</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following table shows our total assets by segment at September 30, 2018 and December 31, 2017 (in thousands), respectively.</div>

<div><br>
</div>

<table id="z1625107514664d5191c089daea4f8ab6" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 70%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="WIDTH: 42%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">Total Assets</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Ionis Core</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Akcea Therapeutics</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Elimination of</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Intercompany Activity</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Total</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 42%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">September 30, 2018</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 12%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,446,425</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 12%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">379,128</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 12%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(577,641</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 12%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,247,913</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 42%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">December 31, 2017 (as revised)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 12%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,342,578</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 12%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">268,804</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 12%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(288,608</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 12%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,322,774</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We have historically funded our operations from collaborations with corporate partners and a relatively small number of partners have accounted for a significant percentage of our revenue. Revenue from significant partners, which is defined as ten percent or more of our total revenue, was as follows:</div>

<div><br>
</div>

<table id="z2a481dbd3404415c9d55597b5e24c7d3" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%; BORDER-COLLAPSE: collapse" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="WIDTH: 40.55%; VERTICAL-ALIGN: bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 30%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" colspan="5">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="WIDTH: 1.77%; VERTICAL-ALIGN: bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 27.68%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" colspan="5">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
</tr>

<tr>
<td style="WIDTH: 40.55%; VERTICAL-ALIGN: bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 16.01%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="WIDTH: 1.68%; VERTICAL-ALIGN: bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 12.31%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="WIDTH: 1.77%; VERTICAL-ALIGN: bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 11.61%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="WIDTH: 1.83%; VERTICAL-ALIGN: bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 14.24%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
</tr>

<tr>
<td style="WIDTH: 40.55%; VERTICAL-ALIGN: bottom">&#160;</td>
<td style="WIDTH: 1.92%; VERTICAL-ALIGN: bottom">&#160;</td>
<td style="WIDTH: 14.09%; VERTICAL-ALIGN: bottom">&#160;</td>
<td style="WIDTH: 1.68%; VERTICAL-ALIGN: bottom">&#160;</td>
<td style="WIDTH: 1.67%; VERTICAL-ALIGN: bottom">&#160;</td>
<td style="WIDTH: 10.64%; VERTICAL-ALIGN: bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: right">(as revised)</div>
</td>
<td style="WIDTH: 1.77%; VERTICAL-ALIGN: bottom">&#160;</td>
<td style="WIDTH: 1.88%; VERTICAL-ALIGN: bottom">&#160;</td>
<td style="WIDTH: 9.73%; VERTICAL-ALIGN: bottom">&#160;</td>
<td style="WIDTH: 1.83%; VERTICAL-ALIGN: bottom">&#160;</td>
<td style="WIDTH: 1.83%; VERTICAL-ALIGN: bottom">&#160;</td>
<td style="WIDTH: 12.42%; VERTICAL-ALIGN: bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: right">(as revised)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 40.55%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Partner A</div>
</td>
<td style="WIDTH: 1.92%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 14.09%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">72%</div>
</td>
<td style="WIDTH: 1.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 1.67%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 10.64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">74%</div>
</td>
<td style="WIDTH: 1.77%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 1.88%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 9.73%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">58%</div>
</td>
<td style="WIDTH: 1.83%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 1.83%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 12.42%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">57%</div>
</td>
</tr>

<tr>
<td style="WIDTH: 40.55%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Partner B</div>
</td>
<td style="WIDTH: 1.92%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 14.09%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">10%</div>
</td>
<td style="WIDTH: 1.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 1.67%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 10.64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">4%</div>
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<td style="WIDTH: 1.77%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
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<td style="WIDTH: 1.88%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
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<td style="WIDTH: 9.73%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">21%</div>
</td>
<td style="WIDTH: 1.83%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 1.83%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
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<td style="WIDTH: 12.42%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">4%</div>
</td>
</tr>

<tr>
<td style="WIDTH: 40.55%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Partner C</div>
</td>
<td style="WIDTH: 1.92%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 14.09%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">5%</div>
</td>
<td style="WIDTH: 1.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 1.67%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 10.64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">8%</div>
</td>
<td style="WIDTH: 1.77%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 1.88%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 9.73%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">10%</div>
</td>
<td style="WIDTH: 1.83%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 1.83%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="WIDTH: 12.42%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">6%</div>
</td>
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<tr>
<td style="WIDTH: 40.55%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Partner D</div>
</td>
<td style="WIDTH: 1.92%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 14.09%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">8%</div>
</td>
<td style="WIDTH: 1.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 1.67%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 10.64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">0%</div>
</td>
<td style="WIDTH: 1.77%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 1.88%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 9.73%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">&#160;3%</div>
</td>
<td style="WIDTH: 1.83%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 1.83%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">&#160;</td>
<td style="WIDTH: 12.42%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">&#160;0%</div>
</td>
</tr>

<tr>
<td style="WIDTH: 40.55%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Partner E</div>
</td>
<td style="WIDTH: 1.92%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 14.09%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">1%</div>
</td>
<td style="WIDTH: 1.68%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 1.67%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 10.64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">0%</div>
</td>
<td style="WIDTH: 1.77%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 1.88%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 9.73%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">1%</div>
</td>
<td style="WIDTH: 1.83%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 1.83%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">&#160;</td>
<td style="WIDTH: 12.42%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">19%</div>
</td>
</tr>
</table>

<div><br>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Contracts receivables from two significant partners comprised approximately 84 percent of our contracts receivables at September 30, 2018 and December 31, 2017.</div>

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<div style="TEXT-ALIGN: justify">
<table id="ze0152a8dd7ff494f9d05ccbaaac14061" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 72pt; VERTICAL-ALIGN: top; FONT-WEIGHT: bold; COLOR: #000000; align: right">ITEM 2</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000">MANAGEMENT&#8217;S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Forward-Looking Statements</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In addition to historical information contained in this Report on Form 10-Q, this Report includes forward-looking statements regarding our business and the therapeutic and commercial potential of SPINRAZA, TEGSEDI, WAYLIVRA 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. 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. These and other risks concerning our programs are described in additional detail in our annual report on Form 10-K for the year ended December 31, 2017, 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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Overview</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We are leaders in discovering and developing RNA-targeted therapeutics. We have created an efficient and broadly applicable drug discovery platform leveraging our expertise in antisense oligonucleotide therapeutics. Using this platform, we have developed a large, diverse and advanced pipeline of potentially first-in-class and/or best-in-class drugs that we believe can provide high value for patients with significant unmet medical needs. In this way, we believe we are fundamentally changing medicine with the goal to transform the lives of those suffering from severe, often life-threatening, diseases.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We made significant progress toward this goal with the commercial launch of SPINRAZA for the treatment of SMA in pediatric and adult patients. SMA is a leading genetic cause of death in infants marked by progressive, debilitating muscle weakness. SPINRAZA became the first and only approved drug to treat people with SMA and is now the standard of care for this debilitating disease. Our partner, Biogen, is responsible for global commercial activities. Since regulatory approval in December 2016, we have earned more than $280 million in commercial revenue from SPINRAZA royalties.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">TEGSEDI is now approved in the U.S., the EU and Canada and Akcea&#8217;s launch activities for TEGSEDI are underway. We believe TEGSEDI has the potential to become the preferred treatment option for many people with hATTR. Our goal is to free these people from the burden of their disease. hATTR is a debilitating, progressive, fatal disease in which patients experience a progressive buildup of amyloid plaque deposits in tissues throughout the body. We licensed TEGSEDI to Akcea, our majority owned affiliate, focused on developing and commercializing drugs to treat patients with rare and serious diseases. By licensing TEGSEDI to Akcea, we believe we will maximize the commercial potential of TEGSEDI, while optimizing our commercial participation. </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">W</font>e estimate that there are approximately 50,000 patients globally with <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">hATTR, the majority of which have symptoms of polyneuropathy</font>.<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> Additionally, we and Akcea are continuing to build our TTR franchise by moving AKCEA-TTR-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> forward rapidly to address the larger patient population, which includes hereditary and wild-type ATTR patients.</font></div>

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<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">31</font></div>

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<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We and Akcea are developing WAYLIVRA to treat two severe and rare, genetically defined diseases, familial chylomicronemia syndrome, or FCS, and familial partial lipodystrophy, or FPL. FCS and FPL are orphan diseases characterized by severely high triglyceride levels that result in severe, daily symptoms and a high risk of life-threatening pancreatitis. We estimate that FCS and FPL each affect 3,000 to 5,000 people globally. The clinical development program for WAYLIVRA consists of three Phase 3 studies called APPROACH, BROADEN and COMPASS. In the first quarter of 2017, we and Akcea reported positive Phase 3 data from the APPROACH study in patients with FCS. In December 2016, we and Akcea reported positive results from the Phase 3 COMPASS study in patients with triglycerides above 500 mg/dL. Based on the positive data from these Phase 3 studies, Akcea filed for marketing authorization for WAYLIVRA in the U.S., EU and Canada in the third quarter of 2017. </font>We and Akcea are in active discussions with EMA and our review process is ongoing. <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">In May 2018, an FDA advisory committee voted in favor of WAYLIVRA for the treatment of FCS. In August 2018, we received a complete response letter from the FDA regarding the New Drug Application, or NDA, for WAYLIVRA. In November 2018, we received a preliminary notification of a notice of noncompliance withdrawal letter from Health Canada for WAYLIVRA. </font>We and Akcea are engaged with the FDA and plan to work with Health Canada to confirm a path forward for WAYLIVRA</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 39.6pt">In addition to commercializing TEGSEDI and preparing to commercialize WAYLIVRA, Akcea is focused on developing their other clinical-stage drugs: AKCEA-APO(a)-<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>, AKCEA-ANGPTL3-L<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> AKCEA-APOCIII-L<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 </font>AKCEA-TTR-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub><sub style="vertical-align: bottom; line-height: 1; font-size: smaller">, </sub>each of which could potentially treat multiple patient populations. Moving these drugs into Akcea allows us to retain substantial value from them and ensures our core focus remains on innovation. As of October 2018, we owned approximately 76 percent of Akcea.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We are addressing a broad spectrum of diseases that affect millions of people, such as cardiovascular disease, clotting disorders, Alzheimer&#8217;s and Parkinson&#8217;s disease. We also are addressing rare diseases, such as acromegaly, familial amyotrophic lateral sclerosis, beta-thalassemia and Huntington&#8217;s disease. We anticipate at least three of our drugs will enter pivotal studies before the end of 2019, representing our next wave of commercial opportunities. These drugs include IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>, for patients with Huntington&#8217;s disease, AKCEA-TTR-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>, our LICA version of TEGSEDI for patients with all forms of TTR amyloidosis and AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> for patients with high Lp(a) who are at risk for cardiovascular disease. We are also focusing on our Ionis-owned drugs that have the potential to move quickly toward the market, including IONIS-GHR-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> for patients with acromegaly.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 39.6pt">We have established alliances with a cadre of leading global pharmaceutical companies that are working alongside us in developing our drugs, advancing our technology and preparing to commercialize our products. Our partners bring substantial resources and expertise that augment and build upon our internal capabilities.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 39.6pt">One of our partners is Biogen with which we have a strategic partnership. In April 2018, we and Biogen entered into a new strategic collaboration to develop novel antisense drug candidates for a broad range of neurological diseases. We received $1 billion from Biogen, comprised of $625 million to purchase our stock at a 25 percent cash premium and $375 million in an upfront payment. We also have partnerships with AstraZeneca, Bayer, GSK, Janssen, Novartis and Roche. Each of these companies brings significant expertise and global resources to develop and potentially commercialize the drugs under these partnerships. Lastly, we also work with a group of companies that can develop our drugs and utilize our technologies outside our primary areas of focus. We refer to these companies as satellite companies.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Through our partnerships, we have created a broad and sustaining base of research and development, or R&amp;D, revenue in the form of license fees, upfront payments and milestone payments while spending prudently to advance our pipeline and technology. Moreover, we have the potential to earn more than $20 billion in future milestone payments and licensing fees from our current partnerships. In late 2016, we began adding commercial revenue from SPINRAZA royalties to our existing R&amp;D revenue base. Looking forward, we have the potential to increase our commercial revenue from SPINRAZA royalties </font>from the continued growth we expect in the U.S., EU and in other markets globally<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">. As a result of the FDA&#8217;s, EMA&#8217;s and Health Canada&#8217;s approval of TEGSEDI, we expect to add product sales from TEGSEDI to our commercial revenue in the fourth quarter. </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We will further increase our commercial revenue if TEGSEDI is approved in additional markets and from WAYLIVRA, assuming it is approved. We also have the potential to share in the future commercial success of our inventions and drugs resulting from our partnerships through royalties, which can further increase our commercial revenue.</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Financial Highlights</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following is a summary of our financial results (in thousands):</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
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</tr>

<tr>
<td style="VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: top; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: top; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: top; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: top; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">Total revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">145,395</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">118,314</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">407,559</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">346,387</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">Total operating expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">163,967</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">107,002</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">479,716</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">309,140</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">Income (loss) from operations</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(18,572</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,312</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(72,157</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">37,247</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">Net loss</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(20,365</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,493</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(87,747</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,616</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(4,559</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2,611</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(46,335</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,266</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">32</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our revenue for the nine months ended September 30, 2018 was $408 million and increased compared to the same period in 2017, primarily from increased commercial revenue from SPINRAZA royalties. We expect to add product revenue from TEGSEDI this year.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our operating expenses for the <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">nine months ended September 30, 2018</font> were $480 million and increased compared to $309 million for the same period in 2017. The increase in operating expenses was primarily due to higher SG&amp;A expenses as we prepared to commercialize <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">TEGSEDI and WAYLIVRA</font>. Our SG&amp;A expenses also increased in the first nine months of 2018 compared to 2017 because of fees we owed under our in-licensing agreements related to SPINRAZA. As sales for SPINRAZA grow, our in-licensing expenses also increase but not at the same rate. We earn tiered royalties on annual SPINRAZA sales and pay nominal fixed third-party royalties that are not tiered. R&amp;D expenses accounted for a smaller portion of the increase in operating expenses. In the fourth quarter of 2018, we expect our operating expenses to continue to increase primarily related to the commercialization of <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">TEGSEDI</font>.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">During the first nine months of 2018, we received more than $1.3 billion in payments from our partners, primarily from Biogen for our 2018 strategic neurology collaboration to develop novel antisense drugs for a broad range of neurological diseases.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold">Recent Events </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic">(Q3 2018 and subsequent activities)</font></div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">Business Highlights</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z8ad9710a6eca4db0a8c6f0f5750e7a0e" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#61623;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic">SPINRAZA</font> &#8211; <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic">the first and only approved treatment for people with spinal muscular atrophy</font></div>
</td>
</tr>
</table>
</div>

<div style="TEXT-ALIGN: justify">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">SPINRAZA sales continued to grow in the third quarter, both in the U.S. and ex-U.S., with global sales of more than $1 billion for year-to-date 2018, as reported by Biogen</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">Nearly 6,000 SMA patients were on SPINRAZA as of the third quarter</div>
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<table id="z6fc52e86524249f1af20db86cac219e0" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">In the U.S., the number of adult patients on therapy grew by over 20 percent compared to the second quarter. Adult SMA patients, which represent the largest and most undertreated patient segment, accounted for more than 50 percent of start forms in the third quarter</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">Access outside the U.S. expanded with formal reimbursement in 28 markets and continued revenue growth in the EU, Asia Pacific and Latin America</div>
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<table id="za05da0d5e19a498291bbb093c7494182" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic">TEGSEDI (inotersen) &#8211; launched in multiple markets for the treatment of polyneuropathy of hATTR in adult patients</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">TEGSEDI approved in the U.S., EU and Canada</div>
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<table id="z21a90a23ce1b4028a8dd8cd0d2b5e161" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Commercial patients in Germany on TEGSEDI</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">TEGSEDI prescriptions received in the U.S.</div>
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<div style="TEXT-ALIGN: left">
<table id="z254e0e55bd5f44c1beb4f7fa6e1c8abf" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic">WAYLIVRA (volanesorsen) &#8211; under regulatory review for the treatment of people living with FCS</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Preparing for launch in the EU following approval</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Planning to confirm a path forward in the U.S. and Canada</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">Pipeline and Business Progress</div>

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<table id="z86a8a408832b48b8afdc124afab68791" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We and Akcea reported positive top-line data from a Phase 2 study of AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> in people with high levels of Lp(a) and established cardiovascular disease demonstrating robust target reductions and a favorable safety and tolerability profile</div>
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<div style="TEXT-ALIGN: justify">
<table id="z2a3fa341749045468f96cf26f8c7e7ed" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We and Roche entered a new collaboration to develop IONIS-FB-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> for the treatment of people with complement-mediated diseases. We received a $75 million upfront payment and will be eligible for development, regulatory and sales milestone payments and license fees of up to $684 million plus royalties of up to 20 percent on commercial sales</div>
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<div style="TEXT-ALIGN: justify">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Positive Phase 1b/2 data for danvatirsen, in combination with durvalumab was presented at the European Society for Medical Oncology, or ESMO, 2018 Congress, demonstrating a response rate approximately double that of durvalumab alone, based on previous studies in patients with refractory head and neck cancer. We earned a $17.5 million milestone payment because AstraZeneca is advancing the program</div>
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<div style="TEXT-ALIGN: justify">
<table id="z7c199dc4c5b5480aa99b16cc4e03e386" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We completed enrollment in a Phase 2b study of IONIS-FXI<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> in patients with end-stage renal disease on dialysis, with data planned for mid-2019</div>
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<div style="TEXT-ALIGN: justify">
<table id="z54f2654904b84fa69741c990830caa4f" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#61623;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We or our partners initiated clinical studies with IONIS-GHR-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> (Phase 2), IONIS-C9<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> (Phase 1/2), IONIS-FXI-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> and IONIS-AZ4-2.5-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> (Phase 1)</div>
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<table id="ze8050d2da1194c158c5dbf3796993917" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We earned a $10 million milestone payment from AstraZeneca for advancing an undisclosed oncology program into development</div>
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<div style="TEXT-ALIGN: justify">
<table id="z8ea5ec82d4bb4507813914e6756cc670" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We appointed Dr. Michael Hayden and Mr. Peter N. Reikes to our Board of Directors</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Critical Accounting Policies</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 require us to make 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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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:</div>

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<table id="z56138fce024c478fb676075973292076" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Assessing the propriety of revenue recognition and associated deferred revenue;</div>
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<div style="TEXT-ALIGN: justify">
<table id="z8de38ce69010481c88873b89f42d7d5f" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Determining the proper valuation of investments in marketable securities;</div>
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<div style="TEXT-ALIGN: justify">
<table id="z65f59e9c9194424ab2a7959a7873a39c" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#61623;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Determining the appropriate cost estimates for unbilled preclinical studies and clinical development activities;</div>
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<div style="TEXT-ALIGN: justify">
<table id="z20649d9f338c497d9dc4b0e36dd2cb1d" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Estimating the impact of the Tax Act and our net deferred income tax asset valuation allowance;</div>
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<div style="TEXT-ALIGN: justify">
<table id="z80d0dde42afc4608b02bee41c3ca06be" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#61623;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Determining the fair value of convertible debt without the conversion feature; and</div>
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<table id="z6a6289559b8446538728974243fe2df1" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#61623;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Valuing premiums received under our collaborations</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">These critical accounting policies and estimates are included in our Annual Report on Form 10-K for the year ended December 31, 2017 in Item 7, &#8220;Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations.&#8221;</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In the first quarter of 2018, we updated the following critical accounting policy:</div>

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<div style="TEXT-ALIGN: justify">
<table id="z942e3cb79ef6428fbfc0907f69ae1d9f" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#61623;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Assessing the propriety of revenue recognition and associated deferred revenue.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our updated critical accounting policy is as follows:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Revenue Recognition</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><u>Adoption of New Revenue Recognition Accounting Standard (Topic 606)</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In May 2014, the FASB issued accounting guidance on the recognition of revenue from customers. <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">This guidance supersedes the revenue recognition requirements we previously followed in Accounting Standards Codification, or ASC, Topic 605, </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic">Revenue Recognition</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">, or Topic 605, and created a new Topic 606, </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic">Revenue from Contracts with Customers</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">, or Topic 606. </font>Under Topic 606, an entity will recognize revenue when it transfers control of promised goods or services to customers in an amount that reflects what the entity expects to receive in exchange for the goods or services. Further, an entity will recognize revenue upon satisfying the performance obligation(s) under the related contract. We adopted Topic 606 on January 1, 2018 under the full retrospective approach, which required us to revise our prior period revenue. Under Topic 606, we were required to review all of our ongoing collaboration agreements in which we recognized revenue after January 1, 2016. We were required to assess what our revenue would have been for the period from January 1, 2016 to December 31, 2017 under Topic 606. As a result of this analysis, we determined that the cumulative revenue we would have recognized under Topic 606 decreased by $53.6 million. We recorded this amount as a cumulative adjustment to our accumulated deficit as of December 31, 2017. We have labeled our prior period financial statements &#8220;as revised&#8221; to indicate the change required under the accounting rules.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following tables summarize the adjustments we were required to make to amounts we originally reported in 2017 to adopt Topic 606 (in thousands, except per share amounts):</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Condensed Consolidated Balance Sheet</div>

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<table id="zd8bad5d7416046e6b7b0d2e8437bd81c" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0" align="center" border="0">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">At December 31, 2017</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Previously</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Reported under</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 605</div>
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<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 606</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Adjustment</div>
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<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Revised</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Current portion of deferred revenue</div>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">106,465</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">18,871</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">125,336</div>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
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<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Long-term portion of deferred revenue</div>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">72,708</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">35,318</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">108,026</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
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<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Accumulated deficit</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,187,398</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(53,636</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,241,034</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
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<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;&#160;&#160;Noncontrolling interest in Akcea Therapeutics, Inc.</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">87,847</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(3,580</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">84,267</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Total stockholders&#8217; equity</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">418,719</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(53,439</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">365,280</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Condensed Consolidated Statement of Operations</div>

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<table id="zab81c972b8484cc9b36752a267155095" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0" align="center" border="0">
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<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended September 30, 2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
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<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Previously</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Reported under</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 605</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 606</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Adjustment</div>
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<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Revised</div>
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<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
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<tr>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Commercial revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: 8.85pt">SPINRAZA royalties</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">32,890</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">32,890</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: 8.85pt">Licensing and other royalty revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">879</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">848</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,727</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: 17.75pt">Total commercial revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">33,769</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">848</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">34,617</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Research and development revenue under collaborative agreements</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">87,142</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(3,445</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">83,697</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -9pt">Total revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">120,911</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2,597</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">118,314</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Income (loss) from operations</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">13,909</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2,597</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,312</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(4,896</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2,597</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,493</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(976</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,635</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(2,611</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss) per share, basic and diluted</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.00</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.02</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(0.02</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>
</table>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">35</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div><br>
</div>

<table id="zdea79049edd745eda65b8ea5a065c77e" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="10">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended September 30, 2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Previously</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Reported under</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 605</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 606</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Adjustment</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Revised</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Commercial revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: 8.85pt">SPINRAZA royalties</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">60,467</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">60,467</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: 8.85pt">Licensing and other royalty revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4,983</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">656</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,639</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: 17.75pt">Total commercial revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">65,450</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">656</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">66,106</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Research and development revenue under collaborative agreements</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">269,917</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,364</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">280,281</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 27pt; TEXT-INDENT: -9pt">Total revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">335,367</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,020</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">346,387</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Income from operations</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">26,227</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,020</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">37,247</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(12,636</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,020</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,616</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(8,716</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,982</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,266</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss) per share, basic</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.02</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.11</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.13</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss) per share, diluted</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.02</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.11</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.13</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Condensed Consolidated Statement of Cash Flows</div>

<div><br>
</div>

<table id="z5a9efc709cc24da9a9eb2eca971f70b3" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="10">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended September 30, 2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Previously</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Reported under</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 605</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Topic 606</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Adjustment</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">As Revised</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Net income (loss)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(12,636</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,020</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(1,616</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Adjustments to reconcile net income (loss) to net cash provided by operating activities:</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt; TEXT-INDENT: -27.15pt">Deferred contract revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">42,091</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(11,020</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">31,071</div>
</td>
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</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Cash and cash equivalents at beginning of period</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">84,685</div>
</td>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">84,685</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 64%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Cash and cash equivalents at end of period</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">159,184</div>
</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
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<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">159,184</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Under Topic 606, compared to Topic 605, our revenue decreased $2.6 million for the three months ended <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">September 30, 2017</font>, and increased $11.0 million for the <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">nine months ended September 30, 2017</font>. The change in our revenue was primarily due to:</div>

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<div style="TEXT-ALIGN: justify">
<table id="zd3a2cfe3259a453c8ae34ef1242dda6e" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif"><u>A change in how we recognize milestone payments:</u></font> Topic 606 requires us to amortize more of the milestone payments we achieve, rather than recognizing the milestone payments in full in the period in which we achieved the milestone event as we did under Topic 605. This change resulted in an increase of $0.5 million and $27.9 million for the three and nine months ended September 30, 2017, respectively.</div>
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<div><br>
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<div style="TEXT-ALIGN: justify">
<table id="za11a88a889214619828f8ed83bf56c14" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif"><u>A change in how we calculate revenue for payments we are recognizing into revenue over time:</u></font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif"> Under Topic 605, we amortized payments into revenue evenly over the period of our obligations. When we made a change to our estimated completion period, we recognized that change on a prospective basis. Under Topic 606, we are required to use an input method to determine the amount we amortize each reporting period. Each period, we review our &#8220;inputs&#8221; such as our level of effort expended, including the time we estimate it will take us to complete the activities, or costs incurred relative to the total expected inputs to satisfy the performance obligation. For certain collaborations, such as Bayer, Janssen and Novartis, the input method resulted in a change to the revenue we had previously recognized using a straight-line amortization method.</font><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">This change resulted in a decrease of $4.0 million and $17.5 million for the three and nine months ended September 30, 2017, respectively.</font></div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our updated revenue recognition policy reflecting Topic 606 is as follows:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><u>Our Revenue Sources</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 condensed consolidated balance sheet.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We expect to add product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 as a result of TEGSEDI&#8217;s approval in the U.S., EU and Canada. We expect to further increase our commercial revenue if TEGSEDI is approved in additional markets and from WAYLIVRA, assuming it is approved.</font>&#160;<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We will also recognize as commercial revenue future sales milestone payments and royalties we earn under our partnerships.</font></div>

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<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Research and development revenue under collaborative agreements</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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, R&amp;D, services, and manufacturing services.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our collaboration agreements are detailed in Note 6, <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic">Collaborative Arrangements and Licensing Agreements.</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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><u>Steps to Recognize Revenue</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We use a five step process to determine the amount of revenue we should recognize and when we should recognize it. The five step process is as follows:</div>

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<div style="TEXT-ALIGN: left">
<table id="ze4cdb10cec464138b68ec653811651f7" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; align: right">1.</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic">Identify the contract</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left; TEXT-INDENT: 36pt">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</div>

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<div style="TEXT-ALIGN: left">
<table id="z1f3f102cc0e04fcf85f9eb5e0546dc99" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We and our partner approved the contract and we are both committed to perform our obligations;</div>
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<div style="TEXT-ALIGN: left">
<table id="zc0a189f8f63f49728df54760da6d4232" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We have identified our rights, our partner&#8217;s rights and the payment terms;</div>
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<div style="TEXT-ALIGN: justify">
<table id="zc8411f428a0245d1a8aaa478dfcf2ab0" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and</div>
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<div style="TEXT-ALIGN: left">
<table id="z15f3cc62bd2d4ad59d132b1f08049803" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: left">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">We believe collectability is probable.</div>
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<div style="TEXT-ALIGN: left">
<table id="zf457f943e7344142b5580212b9d7e833" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; align: right">2.</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: left">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic">Identify the performance obligations</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Often times when we enter into a collaboration agreement in which we provide our partner with an option to license a drug 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 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 drug 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 drug or requests additional goods or services, then we identify a new performance obligation for that item.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z9483f341d80940de9b0cfc2e3180e063" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; align: right">3.</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic">Determine the transaction price</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.</div>

<div><br>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="zb89df424a33c4ea091172ee739189fba" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; align: right">4.</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic">Allocate the transaction price</div>
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</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Estimated future product sales;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Estimated royalties on future product sales;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Contractual milestone payments;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Expenses we expect to incur;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">A discount rate.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We typically estimate the selling price of R&amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;D services include:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">The number of internal hours we estimate we will spend performing these services;</div>
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">The estimated cost of work we will perform;</div>
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">The estimated cost of work that we will contract with third parties to perform; and</div>
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<table id="za717d385f2e5473abd019fe9a477980e" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">The estimated cost of API we will use.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">For purposes of determining the stand-alone selling price of the R&amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</div>

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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; align: right">5.</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic">Recognize revenue</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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; COLOR: #000000">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></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left; TEXT-INDENT: 36pt">The following are examples of when we typically recognize revenue based on the types of payments we receive.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic; TEXT-ALIGN: left; TEXT-INDENT: 36pt"><u>Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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. Our accounting for SPINRAZA royalties did not change as a result of adopting Topic 606.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic; TEXT-ALIGN: left; TEXT-INDENT: 36pt"><u>Research and development revenue under collaboration agreements:</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic; TEXT-ALIGN: left; TEXT-INDENT: 36pt"><u>Upfront Payments</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 new SMA collaboration with Biogen, we received a $25 million upfront payment in December 2017. We allocated the upfront payment to our single performance obligation, R&amp;D services. We are amortizing the $25 million upfront payment using an input method over the estimated period of time we are providing R&amp;D services. Refer to <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Note 6, </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic">Collaborative Arrangements and Licensing Agreements</font>, for further discussion. Under Topic 605, we amortized upfront payments evenly over the period of our obligation.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><u>Milestone Payments</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 drug is approved by the applicable regulator. We will recognize sales based milestone payments in the period we achieve the milestone under the sales-based royalty exception allowed under accounting rules.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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. Under Topic 606, we allocated this payment to our R&amp;D services performance obligation. We are recognizing revenue from this milestone payment over our estimated period of performance. Under Topic 605, this milestone payment was recognized in full in the third quarter of 2017, which was the period in which we achieved the milestone event.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the milestone event. For example, in the third quarter of 2018, we earned a $10 million milestone payment when AstraZeneca initiated a Phase 1 study of IONIS-AZ4-2.5-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>. Our revenue recognition of milestone payments we earn based on our partners&#8217; activities did not change as a result of adopting Topic 606.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><u>License Fees</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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 third quarter of 2018, we earned a $12 million license fee when our majority-owned affiliate, Akcea, <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">entered into an exclusive license agreement with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America</font>. Our recognition of license fees did not change as a result of adopting Topic 606.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Amendments to Agreements</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:</div>

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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">1)</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div>
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<table id="z3b30b865d0cf47ee923378fb691f8c25" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">2)</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">If the goods and/or services are at a stand-alone selling price.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 standalone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> 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;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> 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;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> and to initiate development of IONIS-FXI-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">, 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;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> and IONIS-FXI-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">. 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;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">, 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; COLOR: #000000">Note 6, </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic">Collaborative Arrangements and Licensing Agreements</font>, for further discussion <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">of our accounting treatment for our Bayer collaboration. </font>Our allocation of the consideration we received for the Bayer amendment did not change as a result of adopting Topic 606. However, the method in which we are recognizing revenue related to our R&amp;D services performance obligation did change. We are amortizing revenue related to our R&amp;D services performance obligation using the input method under Topic 606.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Multiple Agreements</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z8139514f39d94e6d840196dfcff044df" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Whether the agreements were negotiated together with a single objective;</div>
</td>
</tr>
</table>
</div>

<div style="TEXT-ALIGN: justify">
<table id="zedc2c0f0948d4dbc9fdbdd76a99a9cb2" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div>
</td>
</tr>
</table>
</div>

<div style="TEXT-ALIGN: justify">
<table id="zdd566ab5707046a4966da4aae94daff7" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">&#9679;</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Whether the goods and/or services promised under the agreements are a single performance obligation.</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 SPA. <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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. Refer to Note 6, </font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic">Collaborative Arrangements and Licensing Agreements</font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> for further discussion of the accounting treatment for the 2018 strategic neurology collaboration with Biogen.</font></div>

<div><br>
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<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">39</font></div>

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</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Results of Operations</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Revenue</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Whenever we refer to prior period results, they reflect the impact of Topic 606, which we adopted in the first quarter of 2018.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Total revenue for the three and nine months ended September 30, 2018 was $145.4 million and $407.6 million, respectively, compared to $118.3 million and $346.4 million for the same periods in 2017 and was comprised of the following (amounts in thousands):</div>

<div><br>
</div>

<table id="z76b6034d75594a11a5d0034fef751fff" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold">(as revised)</font> </div>
</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold">(as revised)</font> </div>
</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">Commercial revenue:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 45pt; TEXT-INDENT: -27pt">SPINRAZA royalties</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9.05%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">70,010</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">32,890</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">167,743</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">60,467</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 45pt; TEXT-INDENT: -27pt">Licensing and other royalty revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9.05%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12,746</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,727</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">14,232</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,639</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 45pt; TEXT-INDENT: -9pt">Total commercial revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9.05%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">82,756</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">34,617</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">181,975</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">66,106</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt; TEXT-INDENT: -9pt">R&amp;D revenue:</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9.05%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt">Amortization from upfront payments</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9.05%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">31,066</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">22,892</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">92,185</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">70,145</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt">Milestone payments</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9.05%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">26,194</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">56,409</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">44,583</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">135,129</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt">License fees</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9.05%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,649</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">424</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">64,227</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">64,942</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt">Other services</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9.05%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,730</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,972</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">24,589</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,065</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 45pt; TEXT-INDENT: -9pt">Total R&amp;D revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9.05%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">62,639</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">83,697</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">225,584</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">280,281</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 81pt; TEXT-INDENT: -9pt">Total revenue</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9.05%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">145,395</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">118,314</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">407,559</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">346,387</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The increase in revenue in the first nine months of 2018 compared to the same period in 2017 was primarily due to increasing commercial revenue from SPINRAZA royalties, which increased over 175 percent. Our R&amp;D revenue for the first nine months of 2018 was significant and demonstrates our ability to generate sustainable revenue from our numerous partnerships.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">R&amp;D revenue from the amortization of upfront payments increased $22.0 million in the first nine months of 2018, compared to the same period in 2017, primarily due to our 2018 strategic neurology collaboration with Biogen which started in the second quarter of 2018. In the fourth quarter of 2018, we will add amortization revenue from our new collaboration with Roche to develop IONIS-FB-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our 2018 R&amp;D revenue from milestone payments was bolstered by two $10 million milestone payments in the third quarter, one from Biogen and one from AstraZeneca. In the same period of 2017, R&amp;D revenue from milestone payments included&#160;$90 million&#160;of milestone payments from Biogen for SPINRAZA approval in the EU and Japan.&#160;Already in the fourth quarter of 2018, we have earned nearly $30 million in milestone payments from AstraZeneca.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Operating Expenses</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Operating expenses for the three and nine months ended September 30, 2018 were $164.0 million and $479.7 million, respectively, and increased compared to $107.0 million and $309.1 million for the same periods in 2017. Our operating expenses increased year over year principally due to higher SG&amp;A expenses as we prepared to commercialize TEGSEDI and WAYLIVRA. Our SG&amp;A expenses also increased year over year because of fees we owed under our in-licensing agreements related to SPINRAZA. </font>As sales for SPINRAZA grow, our in-licensing expenses also increase but not at the same rate. We earn tiered royalties on annual SPINRAZA sales and pay nominal fixed third-party royalties that are not tiered.<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> R&amp;D expenses accounted for a smaller portion of the increase in operating expenses. R&amp;D expenses for the first nine months of 2018 increased, compared to the same period in 2017 primarily due to increases in drug development costs related to several drugs including AKCEA-APO(a)-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> and AKCEA-APOCIII-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">, as we, with Akcea, advanced these programs in development. </font>These increases reflect the investment we are making in advancing and expanding our pipeline. In the fourth quarter of 2018, we expect our operating expenses to continue to increase primarily related to the commercialization of <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">TEGSEDI</font>.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our operating expenses by segment were as follows (in thousands):</div>

<div><br>
</div>

<table id="zb3e3ae694a8449638b9d4b8629cc5c2a" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Ionis Core</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">65,512</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">64,239</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">213,114</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">190,924</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Akcea Therapeutics</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">71,518</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">21,321</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">182,188</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">109,071</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Elimination of intercompany activity</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,946</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(30</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(12,796</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(54,497</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Subtotal</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">129,084</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">85,530</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">382,506</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">245,498</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">34,883</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">21,472</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">97,210</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">63,642</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total operating expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">163,967</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">107,002</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">479,716</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">309,140</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">40</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: left; TEXT-INDENT: 36pt">Research, Development and Patent Expenses</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following table sets forth information on research, development and patent expenses (in thousands):</div>

<div><br>
</div>

<table id="zd2b4b734d13c4ed39a010898a9ec05bd" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Research, development and patent expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">76,475</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">64,033</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">243,455</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">197,915</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">18,780</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">16,181</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">57,698</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">48,443</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total research, development and patent expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">95,255</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">80,214</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">301,153</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">246,358</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our research, development and patent expenses by segment were as follows (in thousands):</div>

<div><br>
</div>

<table id="z66a2722aea5e469e917ed43f1728cacf" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Ionis Core</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">49,452</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">48,776</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">158,860</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">157,363</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Akcea Therapeutics</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">27,068</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">15,287</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">89,940</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">95,049</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Elimination of intercompany activity</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(45</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(30</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(5,345</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(54,497</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Subtotal</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">76,475</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">64,033</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">243,455</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">197,915</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">18,780</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">16,181</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">57,698</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">48,443</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total research, development and patent expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">95,255</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">80,214</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">301,153</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">246,358</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">For the three and nine months ended September 30, 2018, our total research, development and patent expenses were $76.5 million and $243.5 million, respectively, and increased compared to $64.0 million and $197.9 million for the same periods in 2017. The increase in our R&amp;D expenses for the first nine months of 2018, compared to the same period in 2017 was driven primarily by increases in drug development costs related to several drugs including AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub> and AKCEA-APOCIII-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>, as we, with Akcea, advanced these programs in development. All amounts exclude non-cash compensation expense related to equity awards.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; TEXT-INDENT: 36pt"><u>Antisense Drug Discovery</u></div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following table sets forth information on antisense drug discovery expenses (in thousands):</div>

<div><br>
</div>

<table id="z3515e0bc136143c684be49d8d96f4d59" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Antisense drug discovery expenses, excluding non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">14,475</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">14,071</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">41,970</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">39,831</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4,379</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,935</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">13,204</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,644</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total antisense drug discovery expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">18,854</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">18,006</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">55,174</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">51,475</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Antisense drug discovery expenses for the three and nine months ended September 30, 2018 were $14.5 million and $42.0 million, respectively, compared to $14.1 million and $39.8 million for the same periods in 2017. All amounts exclude non-cash compensation expense related to equity awards.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><u>Antisense Drug Development</u></div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following table sets forth research and development expenses for our major antisense drug development projects (in thousands):</div>

<div><br>
</div>

<table id="ze2a6b4dc687541f097419f70f967a496" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">SPINRAZA</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,561</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">WAYLIVRA</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,469</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4,401</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">15,919</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">14,603</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">TEGSEDI</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,373</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4,230</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">14,404</div>
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<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">16,340</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Other antisense development projects</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">21,413</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,183</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">62,580</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">32,852</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Development overhead expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">17,648</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">13,796</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">55,286</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">36,635</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total antisense drug development, excluding non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">45,903</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">33,610</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">148,189</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">110,991</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">8,434</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">6,968</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">25,922</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">20,980</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total antisense drug development expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">54,337</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">40,578</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">174,111</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">131,971</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">41</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Antisense drug development expenses were $45.9 million and $148.2 million for the three and nine months ended September 30, 2018, respectively, and increased compared to $33.6 million and $111.0 million for the same periods in 2017. During the first nine months of 2018, our development expenses for AKCEA-APO(a)-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> and AKCEA-APOCIII-L</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;COLOR: #000000">Rx</sub><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> increased compared to the same period in 2017. We completed enrollment of the Phase 2 clinical study of AKCEA-APO(a)-</font>L<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; COLOR: #000000"> during the first quarter of 2018 and reported positive Phase 2 data in the third quarter of 2018. We also initiated a Phase 2 clinical study of AKCEA-APOCIII-</font>L<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; COLOR: #000000"> in patients with hypertriglyceridemia and established cardiovascular disease in the first quarter of 2018. Slightly offsetting these increases were decreased expenses for SPINRAZA and TEGSEDI. Specifically, we have transitioned all further development of SPINRAZA to Biogen and we completed our Phase 3 TEGSEDI trial in patients with hATTR with polyneuropathy in 2017. All amounts exclude non-cash compensation expense related to equity awards.</font></div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our antisense drug development expenses by segment were as follows (in thousands):</div>

<div><br>
</div>

<table id="z3df46a061a11416a8be3845c88fa987f" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Ionis Core</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">20,821</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">20,521</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">71,767</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">74,655</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Akcea Therapeutics</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">25,082</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">13,089</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">76,422</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">84,730</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Elimination of intercompany activity</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(48,394</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Subtotal</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">45,903</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">33,610</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">148,189</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">110,991</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">8,434</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">6,968</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">25,922</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">20,980</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total antisense drug development expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">54,337</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">40,578</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">174,111</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">131,971</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 "in Phase 1" or "in Phase 2," it does not mean that we are conducting a single, well-defined study with dedicated resources. Instead, we allocate our internal resources on a shared basis across numerous products based on each product'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 drugs in preclinical and early stage clinical research, the fluctuations in expenses from drug to drug, in large part, offset one another. If we partner a drug, it may affect the size of a trial, its timing, its total cost and the timing of the related costs.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><u>Manufacturing and Operations</u></div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our manufacturing and operations expenses were as follows (in thousands):</div>

<div><br>
</div>

<table id="z0e4a03f01d4349249fcc648cf81b1ec5" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Manufacturing and operations expenses, excluding non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">8,085</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">9,167</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">30,083</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">26,260</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr style="HEIGHT: 15px">
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,236</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,693</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">7,024</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,143</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total manufacturing and operations expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,321</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,860</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">37,107</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">31,403</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Manufacturing and operations expenses were $8.1 million and $30.1 million for the three and nine months ended September 30, 2018, respectively, compared to $9.2 million and $26.3 million for the same periods in 2017. Manufacturing and operations expenses increased for the first nine months of 2018. Since accounting rules require us to expense launch supplies prior to obtaining approval, the increase in manufacturing expenses was primarily from the manufacturing of commercial supply of TEGSEDI, prior to its approval in the EU in July 2018. All amounts exclude non-cash compensation expense related to equity awards.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our manufacturing and operations expenses by segment were as follows (in thousands):</div>

<div><br>
</div>

<table id="z3f2a8897b23c4dc89eeae2b4d7a2eb3e" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Ionis Core</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">6,931</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">7,743</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">24,659</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">23,575</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Akcea Therapeutics</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,154</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,424</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,653</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">8,698</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Elimination of intercompany activity</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(5,229</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(6,013</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Subtotal</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">8,085</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">9,167</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">30,083</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">26,260</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,236</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,693</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">7,024</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,143</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total manufacturing and operations expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,321</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,860</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">37,107</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">31,403</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">42</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><u>R&amp;D Support</u></div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In our research, development and patent expenses, we include support costs such as rent, repair and maintenance for buildings and equipment, utilities, depreciation of laboratory equipment and facilities, amortization of our intellectual property, informatics costs, procurement costs and waste disposal costs. We call these costs R&amp;D support expenses.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following table sets forth information on R&amp;D support expenses (in thousands):</div>

<div><br>
</div>

<table id="z610c2d9748484c58985b38020ec6118c" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Personnel costs</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,259</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,608</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">9,456</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">8,174</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Occupancy</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,379</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,132</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">6,281</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">6,086</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Patent expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">513</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">465</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,745</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,459</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Depreciation and amortization</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">115</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">51</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">315</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">175</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Insurance</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">364</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">480</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,991</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,153</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Other</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,382</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,449</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,425</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,786</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total R&amp;D support expenses, excluding non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">8,012</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">7,185</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">23,213</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">20,833</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,731</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,585</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,548</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,676</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total R&amp;D support expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,743</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,770</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">34,761</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">31,509</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">R&amp;D support expenses for the three and nine months ended September 30, 2018 were $8.0 million and $23.2 million, respectively, and were slightly higher compared to $7.2 million and $20.8 million for the same periods in 2017. R&amp;D support expenses increased slightly primarily related to costs associated with the expansion of our business. All amounts exclude non-cash compensation expense related to equity awards.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our R&amp;D support expenses by segment were as follows (in thousands):</div>

<div><br>
</div>

<table id="z564474eff44e4eb0942a4ee8cc14c82a" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Ionis Core</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">7,225</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">6,441</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">20,464</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">19,303</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Akcea Therapeutics</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">832</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">774</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2,865</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,620</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Elimination of intercompany activity</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(45</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(30</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(116</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(90</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Subtotal</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">8,012</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">7,185</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">23,213</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">20,833</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,731</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,585</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,548</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,676</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total R&amp;D support expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,743</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,770</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">34,761</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">31,509</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Selling, General and Administrative Expenses</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Selling, general and administrative expenses include costs associated with the pre-commercialization and commercialization activities for our drugs and costs to support our company, our employees and our stockholders. These costs include personnel and outside costs in the areas of pre-commercialization, commercialization, legal, human resources, investor relations, and finance. Additionally, we include in selling, general and administrative expenses such costs as rent, repair and maintenance of buildings and equipment, depreciation and utilities costs that we need to support the corporate functions listed above. We also include fees we owe under our in-licensing agreements related to SPINRAZA.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; TEXT-INDENT: 36pt">The following table sets forth information on selling, general and administrative expenses (in thousands):</div>

<div><br>
</div>

<table id="z402cd13eb8ce4d47b392149989475f02" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="7">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="3">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Selling, general and administrative expenses, excluding non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">52,609</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">21,497</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">139,051</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">47,583</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">16,103</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,291</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">39,512</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">15,199</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total selling, general and administrative expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">68,712</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">26,788</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">178,563</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">62,782</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">Selling, general and administrative expenses were $52.6 million and $139.1 million for the three and nine months ended September 30, 2018, respectively, and increased compared to $21.5 million and $47.6 million for the same periods in 2017. </font>The increase in SG&amp;A expenses was principally due to the cost of preparing<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#160;</font>to commercialize <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">TEGSEDI and WAYLIVRA</font>, and an increase in the fees we owed under our in-licensing<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#160;</font>agreements related to SPINRAZA. We project our expenses will increase as we launch TEGSEDI and continue to prepare to launch WAYLIVRA.<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> All amounts exclude non-cash compensation expense related to equity awards.</font></div>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">43</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our selling, general and administrative expenses by segment were as follows (in thousands):</div>

<div><br>
</div>

<table id="za5ccb23b1cd14a9f90c51fad788ff652" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Ionis Core</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">16,060</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">15,463</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">54,254</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">33,561</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Akcea Therapeutics</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">44,450</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">6,034</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">92,248</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">14,022</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Elimination of intercompany activity</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,901</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">(7,451</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Subtotal</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">52,609</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">21,497</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">139,051</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">16,103</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,291</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">39,512</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">15,199</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total selling, general and administrative expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">68,712</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">26,788</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">178,563</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">62,782</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: left; TEXT-INDENT: 36pt">Akcea Therapeutics, Inc.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following table sets forth information on&#160;operating expenses (in thousands) for our Akcea Therapeutics business segment:</div>

<div><br>
</div>

<table id="z6fe93197b317467280ac6736eee5bd5e" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Development and patent expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">27,068</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">15,287</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">89,940</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">95,049</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Selling, general and administrative expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">44,450</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">6,034</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">92,248</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">14,022</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total operating expenses, excluding non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">71,518</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">21,321</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">182,188</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">109,071</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Non-cash compensation expense related to equity awards</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12,731</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4,692</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">31,240</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,814</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total Akcea Therapeutics operating expenses</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">84,249</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">26,013</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">213,428</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">120,885</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Operating expenses for Akcea were $71.5 million and $182.2 million for the three and nine months ended September 30, 2018, respectively, and increased compared to $21.3 million and $109.1 million for the same periods in 2017.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In the first nine months of 2017, $48.4 million of development and patent expenses was for one-time sublicensing expenses related to the Novartis collaboration recorded in the first quarter of 2017. $33.4 million of these expenses were non-cash and the remaining $15 million was paid to us. Excluding the $48.4 million of one-time expenses, Akcea&#8217;s development and patent expenses increased $43.3 million in the nine months of 2018 compared to the same period in 2017 as Akcea made investments in advancing its pipeline, including AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>, and AKCEA-APOCIII-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller">Rx</sub>.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">For each period presented, we allocated a portion of Ionis&#8217; R&amp;D support expenses, which are included in development and patent expenses in the table above, to Akcea for work we performed on behalf of Akcea.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Akcea&#8217;s SG&amp;A expenses increased in the first nine months of 2018 compared to the same period in 2017, primarily due to Akcea continuing to build its commercial infrastructure and advance the pre-commercialization activities necessary to successfully launch TEGSEDI and WAYLIVRA. For each period presented, we allocated a portion of Ionis' G&amp;A expenses, which were included in Akcea&#8217;s G&amp;A expenses in the table above, to Akcea for work we performed on Akcea&#8217;s behalf.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">All amounts exclude non-cash compensation expense related to equity awards.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Investment Income</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Investment income for the three and nine months ended September 30, 2018 was $10.0 million and $18.7 million, respectively, compared to $2.8 million and $7.5 million for the same periods in 2017. The increase in investment income was primarily due to our significantly higher average cash balance and an improvement in the market conditions during the first nine months of 2018 compared to the same period in 2017.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Interest Expense</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Interest expense for the three and nine months ended September 30, 2018 was $11.3 million and $33.3 million, respectively, compared to $10.8 million and $34.0 million for the same periods in 2017.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Interest expense includes non-cash amortization of the debt discount and debt issuance costs plus interest expense payable in cash for our 1 percent and 2&#190; percent notes, non-cash interest expense related to the long-term financing liability, which was replaced by mortgage debt for our primarily R&amp;D and manufacturing facilities beginning in July 2017 and other miscellaneous debt.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">In July 2017, </font>we purchased the building that houses our primary R&amp;D facility and the building that houses our manufacturing facility for $79.4 million and $14.0 million, respectively. As a result of the purchase of our primary R&amp;D facility, we <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">extinguished the financing liability we had previously recorded on our balance sheet. </font>We financed the purchase of the buildings with mortgage debt of $51.3 million with an interest rate of 3.88 percent for our primary R&amp;D facility and mortgage debt of $9.1 million with an interest rate of 4.2 percent for our manufacturing facility. Both mortgages mature in August 2027. The non-cash interest expense for our long-term financing liability was replaced with lower mortgage interest expense.</div>

<div><br>
</div>

<div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
<div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="FONT-SIZE: 8pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; FONT-STYLE: normal">44</font></div>

<div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
<hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade">
</div>
</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; TEXT-INDENT: 36pt">The following table sets forth information on interest expense (in thousands):</div>

<div><br>
</div>

<table id="z8f5b107c498b4d758eec8d2088c8659a" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 80%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Three Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="6">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Nine Months Ended</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">September 30,</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2018</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">2017</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Convertible notes:</div>
</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom" valign="bottom" colspan="2">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 18pt">Non-cash amortization of the debt discount and debt issuance&#160;costs</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">8,856</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">8,208</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">26,072</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">24,165</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: 9pt">Interest expense payable in cash</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,714</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,714</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,141</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5,373</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Non-cash interest expense for long-term financing liability</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">308</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3,660</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Interest on mortgage for primary R&amp;D and manufacturing facilities</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">607</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">505</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1,802</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">505</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Other</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">105</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">90</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">317</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">263</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 52%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 9pt; TEXT-INDENT: 9pt">Total interest expense</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">11,282</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10,825</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">33,332</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">33,966</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Net Loss</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We had a net loss of $20.4 million and $87.7 million for the three and nine months ended September 30, 2018, respectively, compared to $7.5 million and $1.6 million for the same periods in 2017. In 2018, the increase in our net loss was primarily due to increased operating expenses as we prepared to commercialize TEGSEDI and WAYLIVRA.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; FONT-STYLE: italic; TEXT-ALIGN: left; TEXT-INDENT: 36pt">Net Loss Attributable to Noncontrolling Interest in Akcea Therapeutics, Inc.&#160;</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Prior to Akcea&#8217;s <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">initial public offering, or IPO,</font> 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 <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">68 percent </font>of Akcea. In the second and third 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. We reflected the increase in our ownership in these financial statements. Our noncontrolling interest in Akcea for the three and <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">nine months ended September 30, 2018</font> was $15.8 million and $41.4 million, respectively, compared to $4.9 million for each of the same periods in 2017.&#160;We also have a corresponding account on our consolidated balance sheet called &#8220;Noncontrolling interest in Akcea Therapeutics, Inc.&#8221; The net loss attributable to noncontrolling interest in Akcea increased during the first nine months of 2018 because we owned between approximately 68 percent and 75 percent during the entire period, compared to the first nine months of 2017 when we owned 100 percent of Akcea until its IPO in July 2017. Akcea&#8217;s increased net loss also contributed to the year-over-year increase in net loss attributable to noncontrolling interest.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; FONT-STYLE: italic; TEXT-ALIGN: left; TEXT-INDENT: 36pt">Net Income (Loss) Attributable to Ionis Pharmaceuticals, Inc. Common Stockholders<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> and Net Income (Loss) per Share</font></div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We had a net loss attributable to our common stockholders&#8217; of $4.6 million for the three months ended <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">September 30, 2018</font>, compared to $2.6 million for the same period in 2017. For the nine months ended <font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">September 30, 2018 </font>we reported a net loss attributable to our common stockholders of $46.3 million, compared to net income attributable to our common stockholders of $3.3 million for the same period in 2017.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">For the three months ended September 30, 2018, basic and diluted net loss per share were $0.03, compared to $0.02 for the same period in 2017. For the nine months ended September 30, 2018, basic and diluted net loss per share were $0.33, compared to basic and diluted net income per share of $0.51 and $0.13 for the same periods in 2017, respectively.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Liquidity and Capital Resources</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We have financed our operations with revenue primarily from research and development collaborative agreements. Beginning in December 2016 we added commercial revenue from SPINRAZA royalties. From our inception through September 30, 2018, we have earned approximately $3.0 billion in revenue.&#160;We have also financed our operations through the sale of our equity securities and the issuance of long-term debt. From the time we were founded through September 30, 2018, we have raised net proceeds of approximately $1.7 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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">At September 30, 2018, we had cash, cash equivalents and short-term investments of $2.0 billion and stockholders&#8217; equity of $840.1 million. In comparison, we had cash, cash equivalents and short-term investments of $1.0 billion and stockholders&#8217; equity of $365.3 million at December 31, 2017.&#160;Our cash, cash equivalents and short-term investments increased in the first nine months of 2018 primarily from the $1 billion payment we received from Biogen for our 2018 strategic neurology collaboration.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">At September 30, 2018, we had consolidated working capital of $1.8 billion compared to $925.1 million at December 31, 2017. As of September 30, 2018, our debt and other obligations totaled $764.9 million compared to $759.7 million at December 31, 2017.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The following table summarizes our contractual obligations as of September 30, 2018. 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:</div>

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</div>

<table id="z6346a3d65ea84140b8384e909b41fb19" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">&#160;</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="18">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Payments Due by Period (in millions)</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">Contractual Obligations (selected&#160;balances&#160;described&#160;below)</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Total</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Less than 1 year</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">1-3 years</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">3-5 years</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">After 5 years</div>
</td>
<td style="VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 40%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Convertible senior notes (principal and interest payable)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">709.4</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">6.9</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">13.7</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">688.8</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 40%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Building mortgage payments</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">81.4</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">2.4</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">4.8</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5.9</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">68.3</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 40%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Financing arrangements (principal and interest payable)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12.8</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12.8</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">&#8212;</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 40%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Other obligations (principal and interest payable)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">1.1</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.1</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.1</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.1</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">0.8</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 40%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Operating leases</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">26.6</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">3.1</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5.9</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">5.2</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 2px solid; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">12.4</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 40%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 10pt; TEXT-INDENT: -10pt">Total</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">831.3</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">25.3</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">24.5</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">700.0</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 9%; VERTICAL-ALIGN: bottom; BORDER-BOTTOM: #000000 4px double; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">81.5</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 4px; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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; COLOR: #000000">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></div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">1 Percent Convertible Senior Notes</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 September 30, 2018, we had a nominal amount of our 2&#190; percent convertible senior notes outstanding. At September 30, 2018, we had the following 1 percent convertible senior notes outstanding (amounts in millions except price per share data):</div>

<div><br>
</div>

<table id="z41ac064e5e29490fa020ac35a0f69a75" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 70%" cellspacing="0" cellpadding="0" align="center" border="0">
<tr>
<td style="WIDTH: 65%; VERTICAL-ALIGN: top; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: top; BORDER-BOTTOM: #000000 2px solid" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">1 Percent Convertible</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Senior Notes</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; PADDING-BOTTOM: 2px; TEXT-ALIGN: left" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 65%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">Outstanding principal balance</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 20%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">685.5</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 65%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">Original issue date ($500 million of principal)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">November 2014</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 65%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">Additional issue date ($185.5 million of principal)</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">December 2016</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 65%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">Maturity date</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">November 2021</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 65%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">Interest rate</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom" colspan="2">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: right">1 percent</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 65%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">Conversion price per share</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #ffffff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">$</div>
</td>
<td style="WIDTH: 20%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #ffffff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">66.81</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #ffffff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>

<tr>
<td style="WIDTH: 65%; VERTICAL-ALIGN: top; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; MARGIN-LEFT: 9pt; TEXT-INDENT: -9pt">Total shares of common stock subject to conversion</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom">&#160;</td>
<td style="WIDTH: 20%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: right; BACKGROUND-COLOR: #cceeff" valign="bottom">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">10.3</div>
</td>
<td style="WIDTH: 1%; VERTICAL-ALIGN: bottom; TEXT-ALIGN: left; BACKGROUND-COLOR: #cceeff" valign="bottom" nowrap="nowrap">&#160;</td>
</tr>
</table>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Interest is payable semi-annually for the 1 percent notes. 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.</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Financing Arrangements</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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:</div>

<div><br>
</div>

<div>
<table id="z0f2f93ee014748f7a9e1c7dc71a594e0" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 58.5pt; VERTICAL-ALIGN: top; align: right">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt">(i)</div>
</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">a floating rate equal to the one-month London Interbank Offered Rate, or LIBOR, in effect plus 1.25 percent per annum;</div>
</td>
</tr>
</table>
</div>

<div>
<table id="z75d67e1493904841bc63fa0585ff4c4f" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 58.5pt; VERTICAL-ALIGN: top; align: right">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left; MARGIN-LEFT: 36pt">(ii)</div>
</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">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</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">a fixed rate equal to the LIBOR swap rate during the period of the loan.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Additionally, we pay 0.25 percent per annum, payable quarterly in arrears, for any amount unused under the credit facility. As of September 30, 2018 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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The credit agreement includes customary affirmative and negative covenants and restrictions. We are in compliance with all covenants of the credit agreement.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; FONT-STYLE: italic; TEXT-ALIGN: left; TEXT-INDENT: 36pt">Research and Development and Manufacturing Facilities</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">In July 2017, </font>we purchased the building that houses our primary R&amp;D facility and the building that houses our manufacturing facility for $79.4 million and $14.0 million, respectively. 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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In addition to contractual obligations, we had outstanding purchase orders as of September 30, 2018 for the purchase of services, capital equipment and materials as part of our normal course of business.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000">QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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; COLOR: #b5062c">&#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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000">CONTROLS AND PROCEDURES</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We maintain disclosure controls and procedures that are designed to ensure that information we are required to disclose in our Exchange Act reports is recorded, processed, summarized and reported within the time periods specified in the SEC&#8217;s rules and forms, and that such information is accumulated and communicated to our management, including our Chief Executive Officer and Chief Financial Officer, as appropriate, to allow timely decisions regarding required disclosure. We design and evaluate our disclosure controls and procedures recognizing that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance and not absolute assurance of achieving the desired control objectives.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">As of our most recently completed fiscal year and as of the end of the period covered by this Quarterly Report on Form 10-Q, we carried out an evaluation of the effectiveness of the design and operation of our disclosure controls and procedures, as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended, under the supervision and with the participation of our management, including our Chief Executive Officer and Chief Financial Officer. Based on our evaluation, our Chief Executive Officer and Chief Financial Officer concluded that our disclosure controls and procedures were effective as of September 30, 2018. There have been no significant changes in our internal controls or in other factors that could significantly affect internal controls subsequent to September 30, 2018.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 implemented internal controls to ensure we adequately evaluated our contracts and properly assessed the impact of the new revenue recognition accounting guidance we adopted on January 1, 2018 reflected in our financial statements. 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 significant changes in our internal controls over financial reporting that occurred during our latest fiscal quarter and that have materially affected, or are reasonably likely to materially affect, our internal controls over financial reporting.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">PART II &#8212; OTHER INFORMATION</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Gilead Litigation</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In August 2013, Gilead Sciences Inc. filed a suit in the United States District Court of Northern District of California related to United States Patent Nos. 7,105,499 and 8,481,712, which are jointly owned by Merck Sharp &amp; Dohme Corp. and Ionis Pharmaceuticals, Inc.&#160;In the suit Gilead asked the court to determine that Gilead's activities do not infringe any valid claim of the named patents and that the patents are not valid. We and Merck Sharp &amp; Dohme Corp. filed our answer denying Gilead's noninfringement and invalidity contentions, contending that Gilead's commercial sale and offer for sale of sofosbuvir prior to the expiration of the '499 and '712 patents infringes those patents, and requesting monetary damages to compensate for such infringement. In the trial for this case held in March 2016, the jury upheld all ten of the asserted claims of the patents-in-suit. The jury then decided that we and Merck are entitled to four percent of $5 billion in past sales of sofosbuvir. Gilead stated it would appeal the jury&#8217;s finding of validity. In the meantime, Gilead asserted two additional non-jury defenses: waiver and unclean hands. Although the judge rejected the waiver defense, she granted Gilead&#8217;s motion claiming that the patents are unenforceable against it under the doctrine of unclean hands. We believe this ruling is contrary to the relevant law and the facts of the case. Accordingly, in July 2016, together with Merck we appealed the decision to the Court of Appeals for the Federal Circuit. Gilead cross-appealed on the issue of validity. In April 2018, the Court of Appeals issued its ruling affirming the District Court&#8217;s finding of unenforceability based on unclean hands.&#160;Having upheld the ruling that the patents are unenforceable against Gilead, the court did not reach the question of validity. In September 2018, we requested a hearing before the Supreme Court. In that request, we asserted that it was improper for the trial court to overturn the jury verdict on a matter of law on the basis of the equitable defense of unclean hands. Gilead will file its reply brief in the fourth quarter of 2018 and we expect to be notified in 2019 whether the Court will hear our case. Under our agreement with Merck, Merck is responsible for the costs of this suit.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000">RISK FACTORS</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; FONT-STYLE: italic; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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, 2017.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Risks Associated with our Ionis Core and Akcea Therapeutics Businesses</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">If the market does not accept our drugs, including SPINRAZA, WAYLIVRA and TEGSEDI, we are not likely to generate revenues or become consistently profitable.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Even if our drugs are authorized for marketing, including SPINRAZA, WAYLIVRA and TEGSEDI, our success will depend upon the medical community, patients and third-party payors accepting our drugs as medically useful, cost-effective and safe. Even when the FDA or foreign regulatory authorities authorize our or our partners' drugs for commercialization, doctors may not prescribe our drugs to treat patients. We and our partners may not successfully commercialize additional drugs.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Additionally, in many of the markets where we may sell our drugs in the future, if we cannot agree with the government regarding the price we can charge for our drugs, then we may not be able to sell our drugs in that market. Similarly, cost control initiatives by governments or third-party payors could decrease the price received for our drugs or increase patient coinsurance to a level that makes our drugs, including SPINRAZA, WAYLIVRA and TEGSEDI, unaffordable.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The degree of market acceptance for our drugs, including SPINRAZA, WAYLIVRA and TEGSEDI, depends upon a number of factors, including the:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">receipt and scope of marketing authorizations;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">establishment and demonstration in the medical and patient community of the efficacy and safety of our drugs and their potential advantages over competing products;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">cost and effectiveness of our drugs compared to other available therapies;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">patient convenience of the dosing regimen for our drugs; and</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">reimbursement policies of government and third-party payors.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Based on the profile of our drugs, physicians, patients, patient advocates, payors or the medical community in general may not accept and/or use any drugs that we may develop.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">For example, the product label for TEGSEDI in the United States 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; COLOR: #000000">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. Therefore, we expect the product label for WAYLIVRA will require periodic blood monitoring. In each case, these label requirements could negatively affect our ability to attract and retain patients for these drugs. 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 and Akcea plan to have greater involvement with physicians and patients, if we and Akcea cannot effectively maintain patients on TEGSEDI or WAYLIVRA, we may not be able to generate substantial revenue from TEGSEDI or WAYLIVRA sales.</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; 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 drugs, including SPINRAZA, WAYLIVRA and</font>&#160;<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold">TEGSEDI, will not contribute significant revenues.</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 drugs that are:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">priced lower than our drugs;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">reimbursed more favorably by government and other third-party payors than our drugs;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">safer than our drugs;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">more effective than our drugs; or</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">more convenient to use than our drugs.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">These competitive developments could make our drugs, including SPINRAZA, WAYLIVRA and TEGSEDI, obsolete or non-competitive.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Certain of our partners are pursuing other technologies or developing other drugs 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's focus on and commitment to our drugs and, as a result, could delay or otherwise negatively affect the commercialization of our drugs, including SPINRAZA, WAYLIVRA and TEGSEDI.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 drugs, and we will primarily rely on our partners, and Akcea to provide this capability.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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, AVXS-101, RG7916, and LMI070 could compete with SPINRAZA and metreleptin and Gemcabene could compete with WAYLIVRA; patisiran, tafamadis, diflunisal, tolcapone, PRX004 and ALN-TTRsc02 could compete with TEGSEDI. For example, patisiran is approved in the United States and Europe for a similar indication as TEGSEDI.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Following approval, our drugs, including SPINRAZA, WAYLIVRA and TEGSEDI could be subject to regulatory limitations.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Following approval of a drug, 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, WAYLIVRA and TEGSEDI.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">In the United States, TEGSEDI&#8217;s label contains a boxed warning for thrombocytopenia and glomerulonephritis,</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">TEGSEDI requires periodic blood and urine monitoring, and</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">in the United States TEGSEDI is available only through a Risk Evaluation and Mitigation Strategy, or REMS, program.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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. 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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 39.6pt">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 SPINRAZA, WAYLIVRA and TEGSEDI.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">We depend on our collaboration with Biogen for the development and commercialization of SPINRAZA.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We have entered into a collaborative arrangement with Biogen to develop and commercialize SPINRAZA. We entered into this collaboration primarily to:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">fund our development activities for SPINRAZA;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">seek and obtain regulatory approvals for SPINRAZA; and</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">successfully commercialize SPINRAZA.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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's commercialization may be harmed or delayed.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our collaboration with Biogen may not result in the continued successful commercialization of SPINRAZA. If Biogen does not continue to successfully commercialize SPINRAZA, we will receive limited revenues for SPINRAZA.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">If Akcea cannot optimize and maintain effective marketing and sales capabilities or enter into agreements with third&#160;parties to market and sell TEGSEDI, we may not generate product&#160;revenue from TEGSEDI.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 20pt">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 in the initial indications Akcea plans to pursue, Akcea will need to optimize and maintain a specialty sales force in each global region it expects to market TEGSEDI, 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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 20pt">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 delay or preclude TEGSEDI&#8217;s launch. Akcea and its partners, if any, will have to compete with other companies to recruit, hire, train, manage and retain marketing and sales personnel.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 20pt">Akcea has incurred expenses prior to the launch of TEGSEDI to integrate and manage the marketing and sales infrastructure. If regulatory requirements or other factors cause the commercial launch of TEGSEDI to be less successful than expected, Akcea would incur expenses for having invested in these capabilities prior to realizing any significant revenue from sales of TEGSEDI. Akcea&#8217;s sales force and marketing teams may not successfully commercialize TEGSEDI.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 20pt">To the extent we and Akcea decide to rely on third parties to commercialize TEGSEDI in a particular geographic market, such as the collaboration Akcea has with PTC Therapeutics to commercialize TEGSEDI in Latin America, we and Akcea may receive less revenue than if Akcea commercialized TEGSEDI by itself. Further we would have less control over the sales efforts of any other third parties involved in commercializing TEGSEDI.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 20pt">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">If government or other third-party payors fail to provide adequate coverage and payment rates for our drugs, including SPINRAZA, TEGSEDI and WAYLIVRA, our revenue will be limited.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 United States who would fit within our target patient populations for our drugs 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 drugs affordable.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Third-party payors, whether foreign or domestic, or governmental or commercial, are developing increasingly sophisticated methods of controlling healthcare costs. In addition, in the United States, 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 United States and in international markets. For example, in the United States, 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 drugs may not be available or adequate in either the United States or international markets, which would negatively affect the potential commercial success of our products, our revenue and our profits.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">If we or our partners fail to obtain regulatory approval for our drugs, including WAYLIVRA, and additional approvals for SPINRAZA and TEGSEDI, we or our partners cannot sell them in the applicable markets.*</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We cannot guarantee that any of our drugs, including WAYLIVRA, will be considered safe and effective, or will be approved for commercialization. In addition, we cannot guarantee that SPINRAZA and TEGSEDI 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 drugs before they can be approved for sale. We must conduct these studies in compliance with FDA regulations and with comparable regulations in other countries.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We and our partners may not obtain necessary regulatory approvals on a timely basis, if at all, for our drugs. It is possible that regulatory agencies will not approve our drugs including, WAYLIVRA for marketing or additional marketing authorizations for SPINRAZA or TEGSEDI. 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 drugs, including SPINRAZA, WAYLIVRA and TEGSEDI, the agency will not approve the specific drug or will require additional studies, which can be time consuming and expensive and which will delay or harm commercialization of the drug. For example, Akcea received a complete response letter, or CRL, from the FDA and a preliminary notification of a 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. The regulatory authorities in Europe could have a similar response to the marketing authorization application pending in Europe.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Failure to receive marketing authorization for WAYLIVRA or our other drugs, or failure to receive additional marketing authorizations for SPINRAZA or TEGSEDI, or delays in these authorizations could prevent or delay commercial introduction of the drug, and, as a result, could negatively impact our ability to generate revenue from product sales.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">If the results of clinical testing indicate that any of our drugs are not suitable for commercial use we may need to abandon one or more of our drug development programs.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Drug discovery and development has inherent risks and the historical failure rate for drugs is high. Antisense drugs are a relatively new approach to therapeutics. If we cannot demonstrate that our drugs are safe and effective for human use, we may need to abandon one or more of our drug development programs.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In the past, we have invested in clinical studies of drugs that have not met the primary clinical end points in their Phase 3 studies. Similar results could occur in clinical studies for our drugs, including the study of WAYLIVRA in patients with FPL. If any of our drugs in clinical studies, including WAYLIVRA, do not show sufficient efficacy in patients with the targeted indication, it could negatively impact our development and commercialization goals for the drug and our stock price could decline.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Even if our drugs are successful in preclinical and human clinical studies, the drugs may not be successful in late-stage clinical studies.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Successful results in preclinical or initial human clinical studies, including the Phase 2 results for some of our drugs in development, may not predict the results of subsequent clinical studies, including the Phase 3 study of WAYLIVRA in patients with FPL. There are a number of factors that could cause a clinical study to fail or be delayed, including:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">the clinical study may produce negative or inconclusive results;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">regulators may require that we hold, suspend or terminate clinical research for noncompliance with regulatory requirements;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">we, our partners, the FDA or foreign regulatory authorities could suspend or terminate a clinical study due to adverse side effects of a drug on subjects in the trial;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">we may decide, or regulators may require us, to conduct additional preclinical testing or clinical studies;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">enrollment in our clinical studies may be slower than we anticipate;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">people who enroll in the clinical study may later drop out due to adverse events, a perception they are not benefiting from participating in the study, fatigue with the clinical study process or personal issues;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">the cost of our clinical studies may be greater than we anticipate; and</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">the supply or quality of our drugs or other materials necessary to conduct our clinical studies may be insufficient, inadequate or delayed.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">In addition, our current drugs, including SPINRAZA, WAYLIVRA and TEGSEDI, are chemically similar to each other. As a result, a safety observation we encounter with one of our drugs could have, or be perceived by a regulatory authority to have, an impact on a different drug 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 drugs 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 drugs: 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 drug.<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000"> 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></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Any failure or delay in the clinical studies, including the Phase 3 study for WAYLIVRA in patients with FPL, could reduce the commercial potential or viability of our drugs.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">If we cannot manufacture our drugs or contract with a third party to manufacture our drugs at costs that allow us to charge competitive prices to buyers, we cannot market our products profitably.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">To successfully commercialize any of our drugs, 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 drugs, called oligonucleotides, on a commercial scale for the systemic administration of a drug. There are a small number of suppliers for certain capital equipment and raw materials that we use to manufacture our drugs, 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 drugs at a cost or in quantities necessary to make commercially successful products.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Also, manufacturers, including us, must adhere to the FDA'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 drugs, including authorizations for SPINRAZA, WAYLIVRA and TEGSEDI, or result in enforcement action after authorization that could limit the commercial success of our drugs, including SPINRAZA, WAYLIVRA and TEGSEDI.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">We depend on third parties to conduct our clinical studies for our drugs and any failure of those parties to fulfill their obligations could adversely affect our development and commercialization plans.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We depend on independent clinical investigators, contract research organizations and other third-party service providers to conduct our clinical studies for our drugs 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 drugs, including WAYLIVRA and TEGSEDI. 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 drugs, including authorizations for WAYLIVRA or additional authorizations for SPINRAZA and TEGSEDI.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Risks Associated with our Businesses as a Whole</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">We have incurred losses, and our business will suffer if we fail to consistently achieve profitability in the future.*</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Because drug discovery and development requires substantial lead-time and money prior to commercialization, our expenses have generally exceeded our revenue since we were founded in January 1989. As of September 30, 2018, we had an accumulated deficit of approximately $1.3 billion and stockholders&#8217; equity of approximately $840.1 million. Most of the 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. We may incur additional operating losses over the next several years, and these losses may increase if we cannot increase or sustain revenue. We may not successfully develop any additional products or achieve or sustain future profitability.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Our ability to use our net operating loss carryovers and certain other tax attributes may be limited.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">As described above, we have incurred net losses. 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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">As of December 31, 2017, we had federal and California net operating loss carryforwards of approximately $561.1 million and $887.1 million, respectively. The federal net operating loss carryforwards will begin to expire, if not utilized, beginning in 2024. These net operating loss carryforwards could expire unused and be unavailable to offset future income tax liabilities. 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. 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. It is possible that we have experienced an ownership change limitation. 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 is materially limited, it would harm our future operating results by effectively increasing our future tax obligations.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 drugs. 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 drugs could suffer.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our corporate partners are developing and/or funding many of the drugs in our development pipeline. If any of these pharmaceutical companies stops developing and/or funding these drugs, our business could suffer and we may not have, or be willing to dedicate, the resources available to develop these drugs on our own.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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>.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Even with funding from corporate partners, if our partners do not effectively perform their obligations under our agreements with them, it would delay or stop the progress of our drug development and commercial programs.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In addition to receiving funding, we enter into collaborative arrangements with third parties to:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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, Novartis and Roche, these collaborations may not continue or result in commercialized drugs, or may not progress as quickly as we first anticipated.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">For example, a collaborator such as AstraZeneca, Bayer, Biogen, GSK, Novartis or Roche, could determine that it is in its financial interest to:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">pursue alternative technologies or develop alternative products that may be competitive with the drug that is part of the collaboration with us;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">pursue higher-priority programs or change the focus of its own development programs; or</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">choose to devote fewer resources to our drugs than it does for its own drugs.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">If any of these occur, it could affect our partner's commitment to the collaboration with us and could delay or otherwise negatively affect the commercialization of our drugs, including SPINRAZA.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">If we do not progress in our programs as anticipated, the price of our securities could decrease.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 drug 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' expectations, including milestones related to SPINRAZA, WAYLIVRA and TEGSEDI, the price of our securities could decrease.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">If we cannot protect our patents or our other proprietary rights, others may compete more effectively against us.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 United States 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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Intellectual property litigation could be expensive and prevent us from pursuing our programs.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 United States 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. For example, in November 2013 we filed a patent infringement lawsuit against Gilead Sciences Inc. in the United States District Court for the Northern District of California. Intellectual property lawsuits may be costly and may not be resolved in our favor.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">If a third party claims that our drugs 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 United States are filed confidentially for the first 18 months. Moreover, the validity and breadth of biotechnology patents involve complex legal and factual questions for which important legal issues remain.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">If we fail to obtain timely funding, we may need to curtail or abandon some of our programs.*</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Many of our drugs are undergoing clinical studies or are in the early stages of research and development. All 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 September 30, 2018, we had cash, cash equivalents and short-term investments equal to approximately $2.0 billion. If we do not meet our goals to successfully commercialize our drugs, including SPINRAZA, WAYLIVRA and TEGSEDI, or to license our drugs and proprietary technologies, we will need additional funding in the future. Our future capital requirements will depend on many factors, such as the following:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">successful commercialization for SPINRAZA and TEGSEDI;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">marketing approvals for WAYLIVRA;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">the profile and launch timing of our drugs, including WAYLIVRA and TEGSEDI;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">changes in existing collaborative relationships and our ability to establish and maintain additional collaborative arrangements;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">continued scientific progress in our research, drug discovery and development programs;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">the size of our programs and progress with preclinical and clinical studies;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">the time and costs involved in obtaining marketing authorizations; and</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">competing technological and market developments, including the introduction by others of new therapies that address our markets.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 drugs.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">The loss of key personnel, or the inability to attract and retain highly skilled personnel, could make it more difficult to run our business and reduce our likelihood of success.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We are dependent on the principal members of our management and scientific staff. We do not have employment agreements with any of our executive officers that would prevent them from leaving us. The loss of our management and key scientific employees might slow the achievement of important research and development goals. It is also critical to our success that we recruit and retain qualified scientific personnel to perform research and development work. We may not be able to attract and retain skilled and experienced scientific personnel on acceptable terms because of intense competition for experienced scientists among many pharmaceutical and health care companies, universities and non-profit research institutions. In addition, failure to succeed in clinical studies may make it more challenging to recruit and retain qualified scientific personnel.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">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.*</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The market price of our common stock, like that of the securities of many other biopharmaceutical companies, has been and is likely to continue to be highly volatile. These fluctuations in our common stock price may significantly affect the trading price of our securities. During the 12 months preceding September 30, 2018, the market price of our common stock ranged from $39.07 to $65.51 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' reimbursement policies, developments in patent or other proprietary rights, public concern regarding the safety of our drugs and general market conditions.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">We are exposed to potential product liability claims, and insurance against these claims may not be available to us at a reasonable rate in the future or at all.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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, WAYLIVRA and TEGSEDI. 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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Because we use biological materials, hazardous materials, chemicals and radioactive compounds, if we do not comply with laws regulating the protection of the environment and health and human safety, our business could be adversely affected.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Our research, development and manufacturing activities involve the use of potentially harmful biological materials as well as materials, chemicals and various radioactive compounds that could be hazardous to human health and safety or the environment. We store most of these materials and various wastes resulting from their use at our facilities in Carlsbad, California pending ultimate use and disposal. We cannot completely eliminate the risk of contamination, which could cause:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">interruption of our research, development and manufacturing efforts;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">injury to our employees and others;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">liabilities under federal, state and local laws and regulations governing health and human safety, as well as the use, storage, handling and disposal of these materials and resultant waste products.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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. We manufacture the finished drug product for WAYLIVRA and TEGSEDI at third-party contract manufacturers.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">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 drugs.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">We manufacture our research and clinical supplies in a manufacturing facility located in Carlsbad, California. The facilities and the equipment we and our contract manufacturers use to research, develop and manufacture our drugs 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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Our business and operations would suffer in the event of computer system failures.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Despite the implementation of security measures, our internal computer systems, and those of our clinical research organizations, manufacturers, commercial partners and other third parties on which we rely, are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. If issues were to arise and cause interruptions in our operations, it could result in a material disruption of our drug programs. For example, the loss of clinical study data from completed or ongoing clinical studies could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. To the extent that any disruption or security breach were to result in a loss of or damage to our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability and the further development or commercialization of our drugs, including SPINRAZA, WAYLIVRA and TEGSEDI could be harmed or delayed.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Provisions in our certificate of incorporation, other agreements and Delaware law may prevent stockholders from receiving a premium for their shares.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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' rights plan, also called a poison pill, which could make it uneconomical for a third party to acquire our company on a hostile basis. In addition, our board of directors has the authority to fix the rights and preferences of, and issue shares of preferred stock, which may have the effect of delaying or preventing a change in control of our company without action by our stockholders.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The provisions of our convertible senior notes could make it more difficult or more expensive for a third party to acquire us. Upon the occurrence of certain transactions constituting a fundamental change, holders of the notes will have the right, at their option, to require us to repurchase all of their notes or a portion of their notes, which may discourage certain types of transactions in which our stockholders might otherwise receive a premium for their shares over the then current market prices.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">These provisions, as well as Delaware law, including Section 203 of the Delaware General Corporation Law, and other of our agreements, may discourage certain types of transactions in which our stockholders might otherwise receive a premium for their shares over then current market prices, and may limit the ability of our stockholders to approve transactions that they think may be in their best interests.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Future sales of our common stock in the public market could adversely affect the trading price of our securities.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Our business is subject to changing regulations for corporate governance and public disclosure that has increased both our costs and the risk of noncompliance.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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's time to comply with these regulations. In addition, if we cannot continue to comply with the requirements of Section 404 in a timely manner, we might be subject to sanctions or investigation by regulatory authorities, such as the SEC, the Public Company Accounting Oversight Board, or PCAOB, or The Nasdaq Global Select Market. Any such action could adversely affect our financial results and the market price of our common stock.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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 "say on pay" and proxy access. Stockholder activism, the current political environment and the current high level of government intervention and regulatory reform may lead to substantial new regulations and disclosure obligations, which may lead to additional compliance costs and impact the manner in which we operate our business.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: left">The comprehensive tax reform bill could adversely affect our business and financial condition.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">The Tax Act significantly revises the Internal Revenue Code of 1986, as amended. The Tax Act, among other things, contains significant changes to corporate taxation, including reduction of the corporate tax rate from a top marginal rate of 35 percent to a flat rate of 21 percent, limitation of the tax deduction for interest expense to 30 percent of adjusted earnings (except for certain small businesses), limitation of the deduction for net operating losses to 80 percent of current year taxable income and elimination of net operating loss carrybacks, one time taxation of offshore earnings at reduced rates regardless of whether they are repatriated, elimination of U.S. tax on foreign earnings (subject to certain important exceptions), immediate deductions for certain new investments instead of deductions for depreciation expense over time, and modifying or repealing many business deductions and credits.&#160;Notwithstanding the reduction in the corporate income tax rate, the overall impact of the new federal tax law is uncertain and our business and financial condition could be adversely affected. In addition, it is uncertain if and to what extent various states will conform to the newly enacted federal tax law.&#160;The impact of this tax reform on holders of our common stock is also uncertain and could be adverse. We urge our stockholders to consult with their legal and tax advisors with respect to this legislation and the potential tax consequences of investing in or holding our common stock.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; TEXT-ALIGN: justify">We could be subject to additional tax liabilities.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: justify">Negative conditions in the global credit markets and financial services and other industries may adversely affect our business.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">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.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000">UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Not applicable.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000">DEFAULT UPON SENIOR SECURITIES</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000">MINE SAFETY DISCLOSURES</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Not applicable.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000">OTHER INFORMATION</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Not applicable.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000">EXHIBITS</div>
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; COLOR: #000000; align: right">a.</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">Description of Document</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #0000ff; TEXT-ALIGN: left"><a style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif" href="ex10_1.htm">10.1</a></div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">Second Amendment to Research Collaboration, Option and License Agreement of December 22, 2014, by and between Ionis Pharmaceuticals, Inc. and Janssen Biotech Inc. Portions of this exhibit have been omitted and separately filed with the SEC.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #0000ff; TEXT-ALIGN: left"><a style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif" href="ex31_1.htm">31.1</a></div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">Certification by Chief Executive Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as amended.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #0000ff; TEXT-ALIGN: left"><a style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif" href="ex31_2.htm">31.2</a></div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">Certification by Chief Financial Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as amended.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #0000ff; TEXT-ALIGN: left"><a style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif" href="ex32_1.htm">32.1*</a></div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">Certification Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">101</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify">The following financial statements from the Ionis Pharmaceuticals, Inc. Quarterly Report on Form 10-Q for the quarter ended September 30, 2018, 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 cash flows and (v) notes to condensed consolidated financial statements (detail tagged).</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000">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.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: bold; COLOR: #000000; TEXT-ALIGN: center">SIGNATURES</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of the Registrant and in the capacities and on the dates indicated.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">/s/ STANLEY T. CROOKE</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Chairman of the Board, President, and Chief Executive Officer</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">Stanley T. Crooke, M.D., Ph.D.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: center">November 6, 2018</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; COLOR: #000000; TEXT-ALIGN: left">/s/ ELIZABETH L. HOUGEN</div>
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<td style="WIDTH: 17.66%; VERTICAL-ALIGN: bottom">&#160;</td>
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<DOCUMENT>
<TYPE>EX-10.1
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; FONT-WEIGHT: bold; TEXT-ALIGN: right"><u>Exhibit 10.1</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: right">CONFIDENTIAL TREATMENT REQUESTED</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: right">UNDER 17 C.F.R. &#167;&#167; 200.80(b)(4), 240.24B-2</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: center">August 7<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;FONT-SIZE: smaller; VERTICAL-ALIGN: text-top; LINE-HEIGHT: 1">th</sup>, 2018</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify">Ionis Pharmaceuticals, Inc.</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify">2855 Gazelle Court</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify">Carlsbad, CA 92010</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify">Attention: Chief Operating Officer</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify">Ionis Pharmaceuticals, Inc.</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify">2855 Gazelle Court</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify">Carlsbad, CA 92010</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify">Attention: General Counsel</div>
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; WIDTH: 36pt; VERTICAL-ALIGN: top; FONT-STYLE: italic; align: right">Re:</td>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; FONT-STYLE: italic"><u>Second Amendment to Research Collaboration, Option and License Agreement of December 22, 2014</u></div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify">Dear Madame or Sir:</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify"><br>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">Reference is made to the Research Collaboration, Option and License Agreement of December 22, 2014 (the &#8220;<font style='FONT-SIZE: 10pt; FONT-FAMILY: "Times New Roman"; FONT-WEIGHT: bold; FONT-STYLE: italic'>Agreement</font>&#8221;),<font style='FONT-SIZE: 10pt; FONT-FAMILY: "Times New Roman"; FONT-WEIGHT: bold'>&#160;</font>by<font style='FONT-SIZE: 10pt; FONT-FAMILY: "Times New Roman"; FONT-WEIGHT: bold'>&#160;</font>and between Janssen Biotech Inc. (&#8220;<font style='FONT-SIZE: 10pt; FONT-FAMILY: "Times New Roman"; FONT-WEIGHT: bold; FONT-STYLE: italic'>JBI</font>&#8221;), and Ionis Pharmaceuticals, Inc. (formerly Isis Pharmaceuticals, Inc.; hereinafter &#8220;<font style='FONT-SIZE: 10pt; FONT-FAMILY: "Times New Roman"; FONT-WEIGHT: bold; FONT-STYLE: italic'>Ionis</font>&#8221;), or individually as &#8220;<font style='FONT-SIZE: 10pt; FONT-FAMILY: "Times New Roman"; FONT-WEIGHT: bold; FONT-STYLE: italic'>Party</font>&#8221; or collectively as &#8220;<font style='FONT-SIZE: 10pt; FONT-FAMILY: "Times New Roman"; FONT-WEIGHT: bold; FONT-STYLE: italic'>Parties</font>.&#8221; Reference is also made to the First Amendment of December 21, 2016 (&#8220;<font style='FONT-SIZE: 10pt; FONT-FAMILY: "Times New Roman"; FONT-WEIGHT: bold; FONT-STYLE: italic'>First Amendment</font>&#8221;) between JBI and Ionis.&#160; This document is a &#8220;<font style='FONT-SIZE: 10pt; FONT-FAMILY: "Times New Roman"; FONT-WEIGHT: bold; FONT-STYLE: italic'>Second Amendment</font>&#8221; to the Agreement and the &#8220;<font style='FONT-SIZE: 10pt; FONT-FAMILY: "Times New Roman"; FONT-WEIGHT: bold; FONT-STYLE: italic'>Second Amendment Effective Date</font>&#8221; shall be the date of the last signature below.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">In general, the Parties agreed to modify the Agreement to reflect alignment on the terms and conditions which will enable JBI to expand the JBI [***] Field to include the [***] delivery of the JBI [***] Development Candidate.</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><br>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify; TEXT-INDENT: 36pt">To effectuate the agreed upon changes, the Parties agree to the provisions described herein.&#160; Defined terms used but not defined herein have the meaning ascribed to such terms in the Agreement.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: left">July, 2018</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: left">Second Amendment</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: left">Page <font style="FONT-WEIGHT: bold">2</font> of <font style="FONT-WEIGHT: bold">3</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; FONT-WEIGHT: bold; FONT-STYLE: italic; TEXT-ALIGN: justify"><u>Agreement Provisions</u></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; FONT-WEIGHT: bold"><u>Confirmation &#8211; Section 3.1</u></font> &#8211; JBI has exercised its Option for the [***] Development Candidate (IONIS-[***]) and has paid the License Fee under Section 6.4.</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><br>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify; TEXT-INDENT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; FONT-WEIGHT: bold"><u>Amendment of Section 4.1.6</u></font> &#8211; The Parties agree that Section 4.1.6 of the Agreement which was added in the First Amendment is hereby deleted in its entirety and replaced with the following:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify; MARGIN-LEFT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; FONT-WEIGHT: bold"><u>[***] Administration of JBI [***] Development Candidate</u></font>. The Parties acknowledge that JBI has elected to expand the JBI [***] Field to include the [***] delivery of the JBI [***] Development Candidate for the treatment of diseases of the gastrointestinal tract (&#8220;<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; FONT-WEIGHT: bold; FONT-STYLE: italic">Expanded GI Field</font>&#8221;) by providing the JRC written notice of such [***] election.</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify; MARGIN-LEFT: 36pt"><br>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify; MARGIN-LEFT: 36pt">In order for JBI to retain its right to develop the JBI [***] Development Candidate in the Expanded GI Field, JBI shall pay an expansion fee of $[***] (&#8220;<font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; FONT-WEIGHT: bold; FONT-STYLE: italic">Expansion Fee</font>&#8221;) to Ionis upon JBI&#8217;s decision to progress the JBI [***] Development Candidate to a [***] [***] with [***] delivery. In the event that Janssen makes the decision to discontinue the development of any and all [***] formulations of the JBI [***] Development Candidate prior to a [***] with [***] delivery, JBI shall pay the expansion fee to Ionis upon the later of (1) [***] and (2) [***].&#160; If JBI has not paid Ionis the Expansion Fee in accordance with this section 4.1.6 by the start of the [***], then JBI&#8217;s right to develop the JBI [***] Development Candidate in the Expanded GI Field will expire. JBI and Ionis will negotiate commercially reasonable terms for managing the continued Development and Commercialization of IONIS-[***]<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;FONT-SIZE: smaller; VERTICAL-ALIGN: bottom; LINE-HEIGHT: 1">&#160;</sub>in the Expanded GI Field in accordance with Section 5.7.</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify; MARGIN-LEFT: 36pt"><br>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify; MARGIN-LEFT: 36pt">If JBI progresses a JBI [***] Development Candidate in the Expanded GI Field, all other provisions of the Agreement shall apply to the Expanded GI Field and, if applicable, Net Sales from [***] delivered and a [***] delivered JBI [***] Development Candidate will be aggregated when calculating payments due under the Agreement royalty tiers.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; FONT-WEIGHT: bold"><u>Amendment of Section 5.7</u></font> - The Parties agree that Section 5.7 which was added in the First Amendment is hereby deleted in its entirety and replaced with the following:</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify; MARGIN-LEFT: 36pt"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; FONT-WEIGHT: bold"><u>Development and Commercialization Cooperation</u></font><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; FONT-WEIGHT: bold">.</font> The Parties will convene to negotiate commercially reasonable terms for managing the continued Development and Commercialization of IONIS-[***] by both Parties, including procedures for the mutual exchange of [***] and [***] information associated with IONIS-[***]<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;FONT-SIZE: smaller; VERTICAL-ALIGN: bottom; LINE-HEIGHT: 1">&#160;</sub>no later than [***] days following the later of (1) [***] or (2) [***].</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: left">Except as otherwise expressly provided herein, the Agreement shall remain in full force and effect without any amendments or modifications.&#160; This Second Amendment may be executed in separate counterparts, each of which, whether delivered by electronic mail, or otherwise is deemed to be an original, and all of which taken together shall constitute one and the same instrument.&#160; This Second Amendment shall be effective as of the Second Amendment Effective Date.&#160; If the above reflects your understanding of the rights and obligations of the Parties under the Agreement, please acknowledge your agreement of the foregoing by executing the countersignature below.</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: left">July, 2018</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: left">Second Amendment</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: left">Page <font style="FONT-WEIGHT: bold">3</font> of <font style="FONT-WEIGHT: bold">3</font></div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: left">Very truly yours,</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; FONT-STYLE: italic; TEXT-ALIGN: left">/s/ Catherine Owen</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: left">Catherine Owen</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: left">President, JBI Biotech, Inc.</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: left">AGREED &amp; ACCEPTED:</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; FONT-STYLE: italic; TEXT-ALIGN: left">/s/ Brett Monia</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: left">Name: <u style='FONT-SIZE: 10pt; FONT-FAMILY: "Times New Roman"'>Brett Monia</u></div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify">Title: <u style='FONT-SIZE: 10pt; FONT-FAMILY: "Times New Roman"'>Chief Operating Officer</u></div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify">Date: August 13, 2018</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman'; TEXT-ALIGN: justify">Ionis Pharmaceuticals, Inc.</div>
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<DOCUMENT>
<TYPE>EX-31.1
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<DESCRIPTION>EXHIBIT 31.1
<TEXT>
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<head>
<title>&#160;</title>
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    Copyright 1995 - 2018 Broadridge-->
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: right">EXHIBIT 31.1</div>

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</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: center">CERTIFICATION</div>

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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify">I, Stanley T. Crooke, certify that:</div>

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<div style="TEXT-ALIGN: justify">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">1.</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">I have reviewed this Quarterly Report on Form 10-Q of Ionis Pharmaceuticals, Inc.;</div>
</td>
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<div><br>
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<div style="TEXT-ALIGN: justify">
<table id="zb6675edb47df4bbea4a0271702e6f654" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="WIDTH: 18pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">2.</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">Based on my knowledge, this quarterly report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this quarterly report;</div>
</td>
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<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z71ee7e73d74b4a3e92f6869e101faf21" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="WIDTH: 18pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">3.</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">Based on my knowledge, the condensed consolidated financial statements, and other financial information included in this quarterly report, fairly present in all material respects the financial condition, condensed consolidated results of operations and condensed consolidated cash flows of the registrant as of, and for, the periods presented in this quarterly report;</div>
</td>
</tr>
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</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z117aba4f4a0344209bd3a40905dd8fe1" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="WIDTH: 18pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">4.</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">The registrant&#8217;s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="zef42d45d28424f0fad98282a3ce7333c" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">a)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z111f1d9e16094d52b2d6d12a31a83ad8" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">b)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z4cb1dd7904d94030ac25de7295e262f6" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">c)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">Evaluated the effectiveness of the registrant&#8217;s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and</div>
</td>
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</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z3f8e6b7cf99b452cae3990af20417b09" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">d)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">Disclosed in this report any change in the registrant&#8217;s internal control over financial reporting that occurred during the registrant&#8217;s most recent fiscal quarter (the registrant&#8217;s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant&#8217;s internal control over financial reporting; and</div>
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</div>

<div style="TEXT-ALIGN: justify">
<table id="z6b872ac534e34de19585d78e9e5d3115" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">5.</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">The registrant&#8217;s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant&#8217;s auditors and the audit committee of registrant&#8217;s board of directors (or persons performing the equivalent functions):</div>
</td>
</tr>
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</div>

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</div>

<div style="TEXT-ALIGN: justify">
<table id="zd5395e4c79094ca79734f7e9f8603410" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">a)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant&#8217;s ability to record, process, summarize and report financial information; and</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z6cdc451656d143b58c59b20f3a92b3ed" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
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<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">b)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant&#8217;s internal control over financial reporting.</div>
</td>
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</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify">&#160;</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left">&#160;</div>

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<td style="WIDTH: 27.75%; VERTICAL-ALIGN: top">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left">Dated: November 6, 2018</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left">&#160;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left">&#160;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left">/s/ STANLEY T. CROOKE</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left">Stanley T. Crooke, M.D., Ph.D.</div>
</td>
<td style="WIDTH: 72.25%; VERTICAL-ALIGN: top">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left">&#160;</div>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left">Chief Executive Officer</div>
</td>
<td style="WIDTH: 72.25%; VERTICAL-ALIGN: top">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: left">&#160;</div>
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<DOCUMENT>
<TYPE>EX-31.2
<SEQUENCE>4
<FILENAME>ex31_2.htm
<DESCRIPTION>EXHIBIT 31.2
<TEXT>
<html>
<head>
<title>&#160;</title>
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<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: right">EXHIBIT 31.2</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: center">CERTIFICATION</div>

<div><br>
</div>

<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; TEXT-ALIGN: justify">I, Elizabeth L. Hougen, certify that:</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z5d8e3659957647c2a3517ae86f4c46ba" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 18pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">1.</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">I have reviewed this Quarterly Report on Form 10-Q of Ionis Pharmaceuticals, Inc.;</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="zc44da378921f4a27bead44d0a9af61c6" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 18pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">2.</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">Based on my knowledge, this quarterly report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this quarterly report;</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z6d292430465b48a69e0318549c45f821" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 18pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">3.</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">Based on my knowledge, the condensed consolidated financial statements, and other financial information included in this quarterly report, fairly present in all material respects the financial condition, condensed consolidated results of operations and condensed consolidated cash flows of the registrant as of, and for, the periods presented in this quarterly report;</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z85743bb094ec43738786ab099109a0eb" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">4.</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">The registrant&#8217;s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z18f12d36473a47f0b5dfddfdb383e0fa" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">a)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z5d18ec07519d44d9bb85e65d37e4e7a8" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">b)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="zc543371401db4259a9fc63406b35527d" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">c)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">Evaluated the effectiveness of the registrant&#8217;s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z11809e7dad27454985c1f71f20a44993" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">d)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">Disclosed in this report any change in the registrant&#8217;s internal control over financial reporting that occurred during the registrant&#8217;s most recent fiscal quarter (the registrant&#8217;s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant&#8217;s internal control over financial reporting; and</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z792a47b97e224277a66399949ef70555" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 18pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">5.</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
<div style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif">The registrant&#8217;s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant&#8217;s auditors and the audit committee of registrant&#8217;s board of directors (or persons performing the equivalent functions):</div>
</td>
</tr>
</table>
</div>

<div><br>
</div>

<div style="TEXT-ALIGN: justify">
<table id="z5bf97c25370e49f2b3ef5b53fdf79036" class="DSPFListTable" style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 100%" cellspacing="0" cellpadding="0">
<tr>
<td style="WIDTH: 36pt"></td>
<td style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; WIDTH: 18pt; VERTICAL-ALIGN: top; align: right">a)</td>
<td style="WIDTH: auto; VERTICAL-ALIGN: top; TEXT-ALIGN: justify">
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  <invest:InvestmentTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 0.1pt;"&gt;3.&amp;#160; Investments&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;As of September 30, 2018, 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&amp;#8217;s, Standard &amp;amp; Poor&amp;#8217;s, or S&amp;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.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following table summarizes the contract maturity of the available-for-sale securities we held as of September 30, 2018:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 60%; border-collapse: collapse;"&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 46.8pt; text-indent: -9pt;"&gt;One year or less&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;80%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 46.8pt; text-indent: -9pt;"&gt;After one year but within two years&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;15%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 46.8pt; text-indent: -9pt;"&gt;After two years but within three years&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; border-bottom: #000000 2px solid; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;5%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 46.8pt; text-indent: -9pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; border-bottom: #000000 4px double; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;100%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;As illustrated above, at September 30, 2018, 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;At September 30, 2018, we had an ownership interest of less than 20 percent in four private companies and one public company 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 company is Antisense Therapeutics Limited.&lt;/div&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;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following is a summary of our investments (in thousands):&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;br /&gt;&lt;/div&gt;&lt;table cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;September 30, 2018&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Cost &lt;/font&gt;(1)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Gains&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; 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background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;840,156&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;143,008&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;2&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(169&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;142,841&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Debt securities issued by the U.S. Treasury (2)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;154,280&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(89&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;154,191&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (2)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;49,873&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(330&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;49,543&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 4.5pt; text-indent: 13.5pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,188,558&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;25&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,852&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,186,731&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;240,208&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,420&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;238,804&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32,435&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(109&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32,326&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;9,872&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(10&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;9,862&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;31,666&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(551&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;31,115&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 4.5pt; text-indent: 13.5pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;314,181&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,090&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;312,107&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 4.5pt; text-indent: 22.5pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,502,739&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;41&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(3,942&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,498,838&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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;table cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;December 31, 2017&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Cost &lt;/font&gt;(1)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Gains&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Losses&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Estimated Fair Value&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Available-for-sale securities:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;500,599&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;2&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(752&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;499,849&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;83,926&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(212&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;83,714&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;29,428&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(17&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;29,411&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (2)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;29,240&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(122&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;29,122&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;643,193&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;6&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,103&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;642,096&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;148,663&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,059&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;147,612&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;52,779&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(168&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;52,611&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,409&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,407&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;65,550&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(740&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;64,810&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;268,401&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,969&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;266,440&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;911,594&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;14&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(3,072&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;908,536&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;(1)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Our available-for-sale securities are held at amortized cost.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;(2)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Includes investments classified as cash equivalents on our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following is a summary of our investments we consider to be temporarily impaired at September 30, 2018. 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-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 30%; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7px; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Less than 12 Months of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Temporary Impairment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;More than 12 Months of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Temporary Impairment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Total Temporary&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Impairment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 30%; vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;(In thousands)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7px; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Number of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Investments&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Estimated&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Unrealized&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Losses&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Estimated&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Unrealized&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Losses&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Estimated&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Unrealized&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Losses&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 30%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7px; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;495&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;889,172&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,687&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;83,706&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(997&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;972,878&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,684&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 30%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7px; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;51&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;132,231&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(139&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;26,862&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(139&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;159,093&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(278&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 30%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7px; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;164,053&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(99&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;164,053&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(99&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 30%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7px; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;48&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;25,687&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(191&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;51,747&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(690&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;77,434&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(881&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 30%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Total temporarily impaired securities&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7px; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;626&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,211,143&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,116&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;162,315&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,826&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,373,458&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(3,942&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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;</invest:InvestmentTextBlock>
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  <!--Collaborative Arrangement Disclosure [Text Block]-->
  <us-gaap:CollaborativeArrangementDisclosureTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;6.&amp;#160; Collaborative Arrangements and Licensing Agreements&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Below, we have included all of our significant collaborations because we adopted Topic 606 on January 1, 2018. We have included new disclosures for each of our collaborations as required under Topic 606.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify;"&gt;Strategic Partnership&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Biogen&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 drugs with Biogen's expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved drug 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;new antisense drugs for the treatment of SMA&lt;/font&gt;. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Additionally, we and Biogen are currently developing six other drugs to treat neurodegenerative diseases under these collaborations, including IONIS-SOD1&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; for ALS, IONIS-MAPT&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx &lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;for Alzheimer&amp;#8217;s disease&lt;/font&gt;&lt;sub style="color: #000000;"&gt;,&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; IONIS-C9&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx &lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;for ALS, and IONIS-BIIB6&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;, IONIS-BIIB7&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; and IONIS-BIIB8&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; to treat undisclosed neurodegenerative diseases. In addition to these drugs, we and Biogen are evaluating numerous additional targets to develop drugs to treat neurological diseases. Most recently, in April 2018, we entered into a new strategic collaboration for the treatment of neurological diseases with Biogen. From inception through September 2018, we have received over $1.9 billion from our Biogen collaborations, including $1 billion we received from Biogen in the second quarter of 2018 when we entered into the 2018 strategic neurology collaboration.&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; text-indent: 36pt;"&gt;SPINRAZA&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In January 2012, we entered into a collaboration agreement with Biogen to develop and commercialize SPINRAZA, an RNA-targeted therapy for the treatment of SMA. In December 2016, the FDA approved SPINRAZA for the treatment of SMA in pediatric and adult patients.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;From inception through September 2018, we earned $717 million in total revenue under our SPINRAZA collaboration, including $281 million in revenue from SPINRAZA royalties and $436 million in R&amp;amp;D revenue. We are receiving tiered royalties ranging from 11 percent to 15 percent on any sales of SPINRAZA. We have exclusively in-licensed patents related to SPINRAZA from Cold Spring Harbor Laboratory and the University of Massachusetts. We pay Cold Spring Harbor Laboratory and the University of Massachusetts a low single digit royalty on sales of SPINRAZA. Biogen is responsible for all further global development, regulatory and commercialization activities and costs for SPINRAZA.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Over the course of our SPINRAZA collaboration, we identified two performance obligations, which were to perform R&amp;amp;D services and to deliver the SPINRAZA license to Biogen. As we achieved milestone payments for our R&amp;amp;D services, we included these amounts in our transaction price for our R&amp;amp;D services performance obligation. We recognized revenue for our R&amp;amp;D services performance obligation over our period of performance through December 2016. We recognized the $75 million license fee for SPINRAZA as revenue when we delivered the license to Biogen in July 2016 because Biogen 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 Biogen.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;We also earned additional milestone payments subsequent to delivering the license to Biogen that we recognized in full in the period each milestone payment became probable because we did not have a performance obligation related to each milestone payment. For example, we received $90 million of milestone payments for the approval of SPINRAZA in the EU and Japan in 2017 and recognized the full amounts into revenue in the period Biogen achieved the milestone events.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Neurology&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In December&amp;#160;2012, we and Biogen entered into a collaboration agreement to develop and commercialize novel antisense drugs to up to three targets to treat neurodegenerative diseases. We are responsible for the development of each of the drugs through the completion of the initial Phase 2 clinical study for such drug. Biogen has the option to license a drug from each of the three programs through the completion of the first Phase 2 study for each program. We are currently advancing IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; for Alzheimer&amp;#8217;s disease under this collaboration. If Biogen exercises its option for a drug, it will assume all further global development, regulatory and commercialization responsibilities and costs for that drug.&amp;#160;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Under the terms of the agreement, we received an upfront payment of $30 million. Over the term of the collaboration, we are eligible to receive up to $210 million in a license fee and milestone payments per program, plus a mark-up on the cost estimate of the Phase 1 and 2 studies. The $210 million per program consists of up to $10 million in development milestone payments, plus a mark-up on the cost estimate of the Phase 1 and 2 studies and up to $130 million in milestone payments if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on sales of any drugs resulting from each of the three programs. From inception through September 2018, we have received $58 million in milestone payments and upfront fees under this collaboration. We will achieve the next payment of $7.5 &lt;/font&gt;million if we continue to advance IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt;.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for Biogen. At inception, we determined the transaction price to be the $30 million upfront payment we received and allocated it to our single performance obligation. As we achieve milestone payments for our R&amp;amp;D services, we include these amounts in our transaction price for our R&amp;amp;D services performance obligation. We are recognizing revenue for our R&amp;amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; currently estimate we will satisfy our performance obligation in &lt;/font&gt;December 2020. From inception through &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;September 2018&lt;/font&gt;, we have included $40 million in total payments in the transaction price for our R&amp;amp;D services performance obligation.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; text-indent: 36pt;"&gt;2013 Strategic Neurology&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In September&amp;#160;2013, we and Biogen entered into a long-term strategic relationship focused on applying antisense technology to advance the treatment of neurodegenerative diseases. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for neurological diseases and has the option to license drugs resulting from this collaboration. The exclusivity for neurological diseases will last through September 2019, and may be extended for any drug development programs Biogen is pursuing under the collaboration. We will usually be responsible for drug discovery and early development of antisense drugs and Biogen will have the option to license antisense drugs after Phase 2 proof of concept. In October 2016, we expanded our collaboration to include additional research activities we will perform. If Biogen exercises its option for a drug, it will assume all further global development, regulatory and commercialization responsibilities and costs for that drug. We are currently advancing five drugs, IONIS-SOD1&lt;sub&gt;Rx&lt;/sub&gt;, IONIS-C9&lt;sub&gt;Rx&lt;/sub&gt;, IONIS-BIIB6&lt;sub&gt;Rx&lt;/sub&gt;, IONIS-BIIB7&lt;sub&gt;Rx&lt;/sub&gt; and IONIS-BIIB8&lt;sub&gt;Rx&lt;/sub&gt; under this collaboration. Biogen will be responsible for all of the drug discovery and development activities for drugs using other modalities.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Under the terms of the agreement, we received an upfront payment of $100 million and are eligible to receive milestone payments, license fees and royalty payments for all drugs developed through this collaboration, with the specific amounts dependent upon the modality of the molecule advanced by Biogen. For each antisense molecule that is chosen for drug discovery and development under this collaboration, we are eligible to receive up to approximately $260 million in a license fee and milestone payments per program. The $260 million per program consists of approximately $60 million in development milestones, including amounts related to the cost of clinical trials, and up to $130 million in milestone payments if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on sales from any antisense drugs developed under this collaboration. If Biogen chooses to advance drugs using other modalities, such as small molecules or monoclonal antibodies, we are eligible to receive up to $90 million in milestone payments per program. The $90 million per program consists of up to $35 million in development milestone payments and up to $55 million in milestone payments if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered single-digit royalties on sales from any drugs using non-antisense modalities developed under this collaboration. From inception through September 2018, we have received over $170 million in upfront fees, milestone payments and other payments under this collaboration, not including a $10 million milestone payment we earned in the third quarter of 2018 for Biogen&amp;#8217;s initiation of a Phase 1 study for IONIS-C9&lt;sub&gt;Rx &lt;/sub&gt;which we received in the fourth quarter of 2018. We will achieve the next payment of up to $10 million if we advance a program under this collaboration.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;At the commencement of our strategic neurology collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for Biogen. At inception, we determined the transaction price to be the $100 million upfront payment we received and allocated it to our single performance obligation. As we achieve milestone payments for our R&amp;amp;D services, we include these amounts in our transaction price for our R&amp;amp;D services performance obligation. We are recognizing revenue for our R&amp;amp;D services performance obligation based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;. &lt;/font&gt;We&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; currently estimate we will satisfy our performance obligation in&lt;/font&gt; September 2019. From inception through &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;September 2018&lt;/font&gt;, we have included $145 million in total payments in the transaction price for our R&amp;amp;D services performance obligation. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;In the third quarter of 2018, we earned a $10 million milestone payment when Biogen initiated a Phase 1 study of IONIS-C9&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;. We recognized this milestone payment in full in the third quarter because we do not have any performance obligations related to this milestone payment. Additionally, we concluded that the payment is not related to our R&amp;amp;D services performance obligation.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;New antisense drugs for the treatment of SMA&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;In December 2017, we entered into a collaboration agreement with Biogen to &lt;/font&gt;identify &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;new antisense drugs for the treatment of SMA&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;. &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Biogen will have the option to license therapies arising out of this collaboration following the completion of preclinical studies. Upon licensing, Biogen &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;will be responsible for all further global development, regulatory and commercialization activities and costs for such therapies&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;. Under the collaboration agreement, we received a&amp;#160;&lt;/font&gt;$25 million&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#160;upfront payment in December 2017. We will receive development and regulatory milestone payments from Biogen if new drugs advance towards marketing approval. &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;In total over the term of our collaboration, we are eligible to receive up to $1.2 billion in license fees, milestone payments and other payments, including up to $80 million for the achievement of development milestones, up to $180 million for the achievement of commercialization milestones and up to $800 million for the achievement of sales milestones. In addition, we are eligible to receive tiered royalties &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;from the mid-teens to &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;mid-20 percent range &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;on net sales.&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; We will achieve the next payment of up to $60 million&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;for the license of a drug under this collaboration. &lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for Biogen. We determined the transaction price to be the $25 million upfront payment we received when we entered into the collaboration. We allocated the transaction price to our single performance obligation. We are recognizing revenue for our R&amp;amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; currently estimate we will satisfy our performance obligation in&lt;/font&gt; December 2020.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; text-indent: 36pt;"&gt;2018 Strategic Neurology Collaboration&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In April 2018, we and Biogen entered into a new strategic collaboration to develop novel antisense drugs for a broad range of neurological diseases and entered into a SPA. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for these diseases for 10 years. We are responsible for the identification of antisense drug candidates based on selected targets, while Biogen will have the option to license therapies arising out of this collaboration and will be responsible for and pay for non-clinical studies, clinical development, manufacturing, and commercialization.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;In the second quarter of 2018, we received &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$1 billion from Biogen, comprised of $&lt;/font&gt;625&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; million to purchase our stock at a 25 percent cash premium and $&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;375&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; million in an upfront payment. &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;We are eligible to receive up to $&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #222222;"&gt;270&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; million for each drug that achieves marketing approval. &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;In addition, we are eligible to receive tiered royalties &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;up to the 20 percent&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; range &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;on net sales.&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; We will achieve the next payment of $7.5 million if Biogen designates a target&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; under this collaboration. &lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;At the commencement of this collaboration, &lt;/font&gt;we identified one performance obligation, which was to perform R&amp;amp;D services for Biogen.&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; We determined our transaction price to be $552 million, comprised of $375 million from the upfront payment and $177 million for the premium paid by Biogen for its purchase of our common stock.&lt;/font&gt; We determined the fair value of the premium we received by using the stated premium in the SPA and applying a lack of marketability discount. We included a lack of marketability discount in our valuation of the premium because Biogen &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;received restricted shares&lt;/font&gt;. We allocated the transaction price to our single performance obligation. We are recognizing revenue for our R&amp;amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; currently estimate we will satisfy our performance obligation in &lt;/font&gt;June 2028.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;SPINRAZA royalties (commercial revenue)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;70.0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32.9&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;167.7&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;60.5&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;34.8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;54.9&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;66.9&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;137.1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -9pt;"&gt;Total revenue from our relationship with Biogen&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;104.8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;87.8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;234.6&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;197.6&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;72&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;74&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;58&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;57&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Our condensed consolidated balance sheet at September 30, 2018 and &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;December 31, 2017 &lt;/font&gt;included deferred revenue of $593.6 million and $93.6 million, respectively, related to our relationship with Biogen.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify;"&gt;Research, Development and Commercialization Partners&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;AstraZeneca&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Cardiac, Renal and Metabolic Diseases Collaboration&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;In July 2015, we and AstraZeneca formed a collaboration to discover and develop antisense therapies for treating cardiac, renal and metabolic diseases. Under our collaboration AstraZeneca has licensed three drugs from us. As part of the agreement, we granted AstraZeneca an exclusive license to IONIS-AZ4-2.5-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;, a drug we designed to treat cardiovascular disease and our first &lt;/font&gt;drug that combines our Generation 2.5 and&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; LIgand-Conjugated Antisense, or LICA, technology. We also granted AstraZeneca the option to license a drug for each additional target advanced under this research collaboration. In February 2018, AstraZeneca licensed a second drug under our collaboration, IONIS-AZ5-2.5&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;, a drug we designed to &lt;/font&gt;treat a genetically associated form of kidney disease&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;. In March 2018, AstraZeneca licensed a third drug under our collaboration, IONIS-AZ6-2.5-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;, a drug we designed to &lt;/font&gt;inhibit an undisclosed target to treat patients with nonalcoholic steatohepatitis, or NASH&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;. AstraZeneca is responsible for all further global development, regulatory and commercialization activities and costs for IONIS-AZ4-2.5-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;, IONIS-AZ5-2.5&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; and&lt;/font&gt;&lt;sub style="color: #000000;"&gt;&amp;#160;&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;IONIS-AZ6-2.5-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; and any other future drugs AstraZeneca licenses.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Under the terms of the agreement, we received a $65 million upfront payment. We are eligible to receive license fees and milestone payments of up to more than $4 billion as drugs under this collaboration advance, including up to $1.1 billion for the achievement of development milestones and up to $2.9 billion for regulatory milestones. In addition, we are eligible to receive tiered royalties up to the low teens on sales from any product that AstraZeneca successfully commercializes under this collaboration agreement. From inception through September 2018, we have received over $165 million in upfront fees, license fees, milestone payments, and other payments under this collaboration, including a $10 million milestone payment we earned in the third quarter of 2018 when AstraZeneca initiated a Phase 1 trial for IONIS-AZ4-2.5-L&lt;sub&gt;Rx&lt;/sub&gt;. We will achieve the next payment of $10 million under this collaboration if we advance a drug under this collaboration&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for AstraZeneca. We determined the transaction price to be the $65 million upfront payment we received and we allocated it to our single performance obligation. We are recognizing revenue for our R&amp;amp;D services performance obligation as we perform services based on our effort to satisfy this performance obligation relative to our total effort expected to satisfy our performance obligation. We&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; currently estimate we will satisfy this performance obligation in&lt;/font&gt; August 2021. As we achieve milestone payments for our R&amp;amp;D services, we include these amounts in our transaction price for our R&amp;amp;D services performance obligation. From inception through &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;September 2018&lt;/font&gt;, we have included $90 million in payments in the transaction price for our R&amp;amp;D services performance obligation.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;We identified separate performance obligations upon AstraZeneca&amp;#8217;s license of IONIS-AZ5-2.5&lt;sub&gt;Rx&lt;/sub&gt; and IONIS-AZ6-2.5-L&lt;sub&gt;Rx&lt;/sub&gt; in the first quarter of 2018 because the licenses are distinct from our other performance obligation and each other. We recognized each $30 million license fee in the first quarter of 2018 because AstraZeneca had full use of the licenses without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the licenses after we delivered them to AstraZeneca.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In the third quarter of 2018, we earned a $10 million milestone payment when AstraZeneca initiated a Phase 1 study of IONIS-AZ4-2.5-L&lt;sub&gt;Rx&lt;/sub&gt;. We recognized this milestone payment in full in the third quarter because we do not have any performance obligations related to this milestone payment. Additionally, we concluded that the payment is not related to our R&amp;amp;D services performance obligation.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Oncology Collaboration&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;In December&amp;#160;2012, we entered into a collaboration agreement with AstraZeneca to discover and develop antisense drugs to treat cancer.&amp;#160;As part of the agreement, we granted AstraZeneca an exclusive license to develop and commercialize &lt;/font&gt;danvatirsen (formerly &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;IONIS-STAT3-2.5&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;) for the treatment of cancer. AstraZeneca is now responsible for all global development, regulatory and commercialization activities for &lt;/font&gt;danvatirsen&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;. We and AstraZeneca have evaluated &lt;/font&gt;danvatirsen&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; in people with head and neck cancer, advanced lymphoma and advanced metastatic hepatocellular carcinoma. AstraZeneca is evaluating &lt;/font&gt;danvatirsen&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; in combination with Imfinzi (durvalumab), AstraZeneca&amp;#8217;s programmed death ligand, or PD-L1, blocking drug, in people with head and neck cancer, metastatic bladder cancer and metastatic non-small cell lung cancer. In addition, we and AstraZeneca established an oncology research program. AstraZeneca has the option to license drugs resulting from the program, and if AstraZeneca exercises its option for a drug, it will be responsible for all further global development, regulatory and commercialization activities and costs for such drug.&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Under the terms of this agreement, we received $31 million in upfront payments. We are eligible to receive milestone payments and license fees from AstraZeneca as programs advance in development. If AstraZeneca successfully develops &lt;/font&gt;danvatirsen&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; and another drug under the research program, we could receive license fees and milestone payments of up to more than $450 million, including up to $152 million for the achievement of development milestones and up to $275 million for the achievement of regulatory milestones.&amp;#160;In addition, we are eligible to receive tiered royalties up to the low to mid-teens on sales from any drugs resulting from these programs. From inception through September 2018, we have received $97.8 million in upfront fees, milestone payments, and other payments under this oncology collaboration, not including nearly $30 million in milestone payments we achieved when AstraZeneca advanced&lt;/font&gt; two programs in the fourth quarter of 2018. We &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;will achieve the next payment of up to $25.0 million &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;if we advance a drug under our cancer research program with AstraZeneca.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;At the commencement of this collaboration, we identified four performance obligations. We determined the transaction price to be the $31 million in upfront payments we received. We allocated the transaction price based on the estimated stand-alone selling price of each of our performance obligations and recognized the associated revenue over the period of our performance. We recognized revenue for three of our obligations over our period of performance, concluding in March 2014. Our remaining performance obligation was to perform R&amp;amp;D services. We allocated $7.6 million to this performance obligation and recognized the associated revenue over the period of our performance, which ended in February 2018. As we achieved milestone payments for our R&amp;amp;D services, we included these amounts in our transaction price for our R&amp;amp;D services performance obligation.&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with AstraZeneca (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;14.2&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4.8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;86.5&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;14.8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;10&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;21&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Our &lt;/font&gt;condensed consolidated balance sheet at &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;September 30, 2018 and December 31, 2017 included deferred revenue of $44.9 million and $57.7 million, respectively, related to our relationship with AstraZeneca.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Bayer&lt;/div&gt;&lt;div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI&lt;sub&gt;Rx&lt;/sub&gt; for the prevention of thrombosis. We were responsible for completing a Phase 2 study of IONIS-FXI&lt;sub&gt;Rx&lt;/sub&gt; in people with end-stage renal disease on hemodialysis. Under the terms of the agreement, we received a $100 million upfront payment in the second quarter of 2015. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI&lt;sub&gt;Rx&lt;/sub&gt; and to initiate development of IONIS-FXI-L&lt;sub&gt;Rx&lt;/sub&gt;, which Bayer licensed. In conjunction with the decision to advance these programs, we received a $75 million payment from Bayer. We are conducting a Phase 2b study evaluating IONIS-FXI&lt;sub&gt;Rx&lt;/sub&gt; in people with end-stage renal disease on hemodialysis to finalize dose selection. Additionally, we plan to develop IONIS-FXI-L&lt;sub&gt;Rx&lt;/sub&gt; through Phase 1. Following these studies and Bayer's decision to further advance these programs, Bayer will be responsible for all global development, regulatory and commercialization activities and costs for both drugs.&amp;#160;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We are eligible to receive additional milestone payments as each drug advances toward the market. In total over the term of this collaboration, we are eligible to receive up to $385 million in license fees, milestone payments and other payments, including up to $125 million for the achievement of development milestones and up to $110 million for the achievement of commercialization milestones. In addition, we are eligible to receive tiered royalties in the low to high 20 percent range on gross margins of both drugs combined. From inception through September 2018, we have received over $175 million from our Bayer collaboration. We will achieve the next payment of $10 million if a program advances under this collaboration.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;At the commencement of this collaboration, we identified three performance obligations. We determined the transaction price to be the $100 million in upfront payment we received. We allocated the transaction price based on the relative stand-alone selling prices of each of our performance obligations and recognized the associated revenue as follows:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognized $91.2 million for the exclusive license of IONIS-FXI&lt;sub&gt;Rx &lt;/sub&gt;in May 2015 because Bayer &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;had full use of the license without any continuing involvement from us&lt;/font&gt;.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognized $4.3 million for the R&amp;amp;D services for IONIS-FXI&lt;sub&gt;Rx&lt;/sub&gt; over the period of our performance, which ended in November 2016.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We allocated $4.5 million for API, which we are recognizing into revenue as we deliver the API.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;In February 2017, when we amended our collaboration with Bayer, we identified two new performance obligations&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;, one for the license of IONIS-FXI-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; and one for R&amp;amp;D services&lt;/font&gt;. We determined the transaction price to be the $75 million payment. We allocated $64.9 million to &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;the license of IONIS-FXI-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; based on its estimated stand-alone selling price and recognized the associated revenue upon our delivery of the license in the first quarter of 2017. We allocated $10.1 million to our R&amp;amp;D services performance obligation based on an estimated stand-alone selling price. &lt;/font&gt;We are recognizing revenue for our R&amp;amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; currently estimate we will satisfy our &lt;/font&gt;R&amp;amp;D services &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;performance obligation in&lt;/font&gt; May 2019.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Bayer (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1.9&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;3.3&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;66.0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;19&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Our condensed consolidated balance sheet at September 30, 2018 and &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;December 31, 2017 &lt;/font&gt;included deferred revenue of $6.0 million and $9.3 million, respectively, related to our relationship with Bayer.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Janssen Biotech, Inc.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In December&amp;#160;2014, we entered into a collaboration agreement with Janssen Biotech, Inc. to discover and develop antisense drugs that can be locally administered, including oral delivery, to treat autoimmune disorders of the gastrointestinal tract. Janssen has the option to license drugs from us through the designation of a development candidate for up to three programs. Prior to option exercise we are responsible for the discovery activities to identify a development candidate. If Janssen exercises an option for one of the programs, it will be responsible for the global development, regulatory and commercial activities under that program. Under the terms of the agreement, we received $35 million in upfront payments. We are eligible to receive up to more than $800 million in license fees and milestone payments for these programs, including up to $175 million for the achievement of development milestones, up to $440 million for the achievement of regulatory milestones and up to $180 million for the achievement of commercialization milestones. From inception through September 2018, we have received $75 million, including $15 million in license fees when Janssen licensed IONIS-JBI1-2.5&lt;sub&gt;Rx&lt;/sub&gt; and IONIS-JBI2-2.5&lt;sub&gt;Rx&lt;/sub&gt; from us in 2016 and 2017, respectively. We also received $5 million in January 2018 for the initiation of a Phase 1 study of IONIS-JBI1-2.5&lt;sub&gt;Rx &lt;/sub&gt;in late 2017. In addition, we are eligible to receive tiered royalties up to the near teens on sales from any drugs resulting from this collaboration. We will achieve the next payment of $5 million if Janssen continues to advance a target under this collaboration.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for Janssen. We determined the transaction price to be the $35 million upfront payments we received. We allocated the &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$35 million&lt;/font&gt; to our single performance obligation. As we achieved milestone payments for our R&amp;amp;D services, we included these amounts in our transaction price for our R&amp;amp;D services performance obligation. We recognized revenue for our R&amp;amp;D services performance obligation over our period of performance, through November 2017.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;We identified separate performance obligations each time Janssen licensed one of our drugs under our collaboration because the licenses we granted to Janssen were distinct from our other performance obligations. We recognized the $10 million license fee for IONIS-JBI1-2.5&lt;sub&gt;Rx&lt;/sub&gt; in July 2016 and $5 million for the license of IONIS-JBI2-2.5&lt;sub&gt;Rx&lt;/sub&gt; in November 2017, because Janssen had full use of the licenses without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the licenses after we delivered them to Janssen.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Janssen (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.9&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;3.4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;6.6&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;18.1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;3&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;2&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We did not have any deferred revenue from our relationship with Janssen at September 30, 2018 or December 31, 2017.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Roche&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; margin-left: 36pt;"&gt;Huntington's Disease&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In April&amp;#160;2013, we formed an alliance with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, to develop treatments for Huntington's disease, or HD, based on our antisense technology. Roche had the option to license the drugs from us through the completion of the first Phase 1 trial. Under the agreement, we are responsible for the discovery and development of an antisense drug targeting huntingtin, or HTT, protein. We evaluated a drug targeting HTT, IONIS-HTT&lt;sub&gt;Rx&lt;/sub&gt;, in a Phase 1/2a clinical study in people with early stage HD.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In December 2017, upon completion of the Phase 1/2a study, Roche exercised its option to license IONIS-HTT&lt;sub&gt;Rx &lt;/sub&gt;and is now responsible for the global development, regulatory and commercialization activities for IONIS-HTT&lt;sub&gt;Rx&lt;/sub&gt;. Under the terms of the agreement, we received an upfront payment of $30 million in April&amp;#160;2013.&amp;#160;In December 2016, we updated development activities for IONIS-HTT&lt;sub&gt;Rx&lt;/sub&gt; and as a result we were eligible for an additional $3 million payment, which we achieved in 2017. We are eligible to receive up to $365 million in a license fee and milestone payments including up to $70 million for the achievement of development milestones, up to $170 million for the achievement of regulatory milestones and up to $80 million for the achievement of commercialization milestones. In addition, we are eligible to receive up to $136.5 million in milestone payments for each additional drug successfully developed.&amp;#160;We are also eligible to receive tiered royalties up to the mid-teens on any sales of any product resulting from this alliance. From inception through September 2018, we have received over $110 million in upfront fees, milestone payments and license fees for advancing IONIS-HTT&lt;sub&gt;Rx&lt;/sub&gt;, including the $45 million license fee we received in January 2018 for IONIS-HTT&lt;sub&gt;Rx&lt;/sub&gt;. We will achieve the next payment of $35 million if Roche initiates a pivotal study for IONIS-HTT&lt;sub&gt;Rx&lt;/sub&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for Roche. We determined the transaction price to be the $30 million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&amp;amp;D services, we included these amounts in our transaction price for our R&amp;amp;D services performance obligation. We recognized revenue for our R&amp;amp;D services performance obligation over our period of performance, through September 2017.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;We identified a second performance obligation upon Roche&amp;#8217;s license of IONIS-HTT&lt;sub&gt;Rx&lt;/sub&gt; in the fourth quarter of 2017 because the license we granted to Roche is distinct from our other performance obligation. We recognized the $45 million license fee for IONIS-HTT&lt;sub&gt;Rx&lt;/sub&gt; as revenue at that time because Roche had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Roche.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;We do not have any remaining performance obligations related to IONIS-HTT&lt;sub&gt;Rx&lt;/sub&gt; under this collaboration with Roche, however we can still earn additional payments and royalties as Roche advances IONIS-HTT&lt;sub&gt;Rx&lt;/sub&gt;.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;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; for Complement-Mediated Diseases&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;In October 2018, we entered into a collaboration agreement with Roche to&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; develop IONIS-FB-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 are exploring the drug in a severe and rare renal indication.&amp;#160;&lt;/font&gt;Roche&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#160;has the option to license IONIS-FB-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#160;at the completion of these studies. Upon licensing,&amp;#160;&lt;/font&gt;Roche &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;will be responsible for all further global development, regulatory and commercialization activities and costs.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Under this new collaboration agreement, we received a&amp;#160;&lt;/font&gt;$75 million&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#160;upfront payment in October 2018. We are eligible to receive up to&amp;#160;&lt;/font&gt;$684 million&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#160;in development, regulatory and sales milestone payments and license fees. In addition, we are also eligible to receive tiered royalties from the high teens to twenty percent on net sales. We will achieve the next payment of $20 million when we advance &lt;/font&gt;the Phase 2 study in patients with dry AMD&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1.8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4.5&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5.4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5.9&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;2&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We did not have any deferred revenue from our relationship with Roche at September 30, 2018 or December 31, 2017.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;GSK&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In March&amp;#160;2010, we entered into an alliance with GSK using our antisense drug discovery platform to discover and develop new drugs against targets for rare and serious diseases, including infectious diseases and some conditions causing blindness. Under the terms of the agreement, we received upfront payments of $35 million.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;GSK is advancing two drugs targeting hepatitis B virus, or HBV, under our collaboration: IONIS-HBV&lt;sub&gt;Rx&lt;/sub&gt;&amp;#160;and IONIS-HBV-L&lt;sub&gt;Rx&lt;/sub&gt;. GSK is currently conducting Phase 2 studies for both of these drugs, which we designed to reduce the production of viral proteins associated with HBV infection. In March 2016, we and GSK amended the development plan for IONIS-HBV&lt;sub&gt;Rx&lt;/sub&gt; to allow GSK to conduct all further development activities for this program. GSK has the exclusive option to license the drugs resulting from this alliance at Phase 2 proof-of-concept for a license fee.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Under our agreement, if GSK successfully develops these drugs and achieves pre-agreed sales targets, we could receive license fees and milestone payments of $262 million, including up to $47.5 million for the achievement of development milestones, up to $120 million for the achievement of regulatory milestones and up to $70 million for the achievement of commercialization milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on sales from any product that GSK successfully commercializes under this alliance. From inception through September 2018, we have received more than $162 million in payments under this alliance with GSK. We will achieve the next payment of up to $25 million if GSK licenses a drug under this program.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for GSK. We determined the transaction price to be the $35 million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&amp;amp;D services, we included these amounts in our transaction price for our R&amp;amp;D services performance obligation. We recognized revenue for our R&amp;amp;D services performance obligation over our period of performance, through March 2015. We do not have any remaining performance obligations under our collaboration with GSK, however we can still earn additional payments and royalties as GSK advances these drugs.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with GSK (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4.6&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1.5&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;14.4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Our revenue for the nine months ended September 30, 2017, was from our work on the programs under our collaboration with GSK. We did not have any deferred revenue from our relationship with GSK at September 30, 2018 or December 31, 2017.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Akcea Collaborations&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following collaboration agreements relate to Akcea, our majority owned affiliate. Our consolidated results include all the revenue earned and cash received under these collaboration agreements. 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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Novartis&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In January 2017, we and Akcea initiated a collaboration with Novartis to develop and commercialize AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt; and AKCEA-APOCIII-L&lt;sub&gt;Rx&lt;/sub&gt;.&lt;sub&gt;&amp;#160;&lt;/sub&gt;Under the collaboration agreement, Novartis has an exclusive option to further develop and commercialize AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt; and AKCEA-APOCIII-L&lt;sub&gt;Rx&lt;/sub&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 drug. If Novartis exercises an option for one of these drugs, Novartis will be responsible for all further global development, regulatory and co-commercialization activities and costs for such drug.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Akcea received a $75 million upfront payment in the first quarter of 2017, of which it retained $60 million and paid us $15 million as a sublicense fee. If Novartis exercises its option for a drug, Novartis will pay Akcea a license fee equal to $150 million for each drug it licenses. In addition, for AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt;, Akcea is eligible to receive up to $600 million in milestone payments, including $25 million for the achievement of a development milestone, up to $290 million for the achievement of regulatory milestones and up to $285 million for the achievement of commercialization milestones. In addition, for AKCEA-APOCIII-L&lt;sub&gt;Rx&lt;/sub&gt;, Akcea is eligible to receive up to $530 million in milestone payments, including $25 million for the achievement of a development milestone, up to $240 million for the achievement of regulatory milestones and up to $265 million for the achievement of commercialization milestones. Akcea is also eligible to receive tiered royalties in the mid-teens to low 20 percent range on net sales of AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt; and AKCEA-APOCIII-L&lt;sub&gt;Rx&lt;/sub&gt;. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Novartis will reduce these royalties upon the expiration of certain patents or if a generic competitor negatively impacts the product in a specific country. &lt;/font&gt;Akcea will pay 50 percent of these license fees, milestone payments and royalties to us as a sublicense fee.&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; Akcea plans to co-commercialize any licensed drug commercialized by Novartis in selected markets under terms and conditions that we plan to negotiate with Novartis in the future, through its specialized sales force.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In conjunction with this collaboration, we and Akcea entered into a SPA with Novartis. As part of the SPA, Novartis purchased 1.6 million shares of our common stock for $100 million in the first quarter of 2017. As part of the SPA, Novartis was required to purchase $50 million of Akcea&amp;#8217;s common stock at the IPO price or our common stock at a premium if an IPO did not occur by April 2018. Under the SPA, in July 2017, Novartis purchased $50 million of Akcea&amp;#8217;s common stock in a separate private placement concurrent with the completion of its IPO at a price per share equal to the IPO price.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;At the commencement of this collaboration, we identified four separate performance obligations:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;R&amp;amp;D services for AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt;;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;R&amp;amp;D services for AKCEA-APOCIII-L&lt;sub&gt;Rx&lt;/sub&gt;;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;API for AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt;; and&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;API for AKCEA-APOCIII-L&lt;sub&gt;Rx&lt;/sub&gt;.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We determined that the R&amp;amp;D services for each drug and the API for each drug were distinct from our other performance obligations.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We determined our transaction price to be $108.4 million, comprised of the following:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$75 million from the upfront payment;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$28.4 million for the premium paid by Novartis for its purchase of our common stock at a premium in the first quarter of 2017; and&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$5.0 million for the potential premium Novartis would have paid if they purchased our common stock in the future.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We allocated the transaction price based on the estimated stand-alone selling price of each performance obligation as follows:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$64.0 million for the R&amp;amp;D services for &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;AKCEA-APO(a)-L&lt;/font&gt;&lt;sub style="font-family: 'Times New Roman';"&gt;Rx&lt;/sub&gt;&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;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$40.1 million for the R&amp;amp;D services for &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;AKCEA-APOCIII-L&lt;/font&gt;&lt;sub style="font-family: 'Times New Roman';"&gt;Rx&lt;/sub&gt;; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$1.5&lt;/font&gt; million for the delivery of AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt; API; and&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$2.8&lt;/font&gt; million for the delivery of AKCEA-APOCIII-L&lt;sub&gt;Rx&lt;/sub&gt; API.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;We are recognizing revenue related to the R&amp;amp;D services for the AKCEA-APO(a)-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; and AKCEA-APOCIII-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; performance obligations as we perform services &lt;/font&gt;based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;. &lt;/font&gt;We&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; currently estimate we will satisfy the significant portion of our performance obligation for AKCEA-APO(a)-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; by December 2018 with the remainder by the end of March 2019. &lt;/font&gt;We&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; currently estimate we will satisfy the significant portion of our performance obligation for AKCEA-APOCIII-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; by June 2019 with the remainder by the end of December 2019. We recognized the amount attributed to the API supply for AKCEA-APO(a)-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; when we delivered it to Novartis in 2017. We recognized the amount attributed to the API supply for AKCEA-APOCIII-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; when we delivered it to Novartis in May 2018.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 consolidated balance sheet.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;7.2&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;9.9&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;42.7&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;21.7&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;10&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;6&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Our condensed consolidated balance sheet at September 30, 2018 and December 31, 2017 included deferred revenue of $34.8 million and $70.7 million, respectively, related to our relationship with Novartis.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;PTC Therapeutics&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In August 2018, Akcea entered into an exclusive license agreement with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America. Under the license agreement, Akcea will receive up to $26 million of payments, including $12 million which it received in the third quarter of 2018, $6 million upon the earlier of FDA or EMA approval of WAYLIVRA and up to $8 million of regulatory milestone payments. Akcea will receive royalties from PTC in the mid-20 percent range on net sales in Latin America for each drug.&amp;#160;PTC's obligation to pay Akcea royalties begins on the earlier of 12 months after the first commercial sale of a product in&amp;#160;Brazil&amp;#160;or the date that PTC recognizes revenue of at least&amp;#160;$10 million&amp;#160;in Latin America. These royalties may be reduced upon expiration of certain patents or if a generic competitor negatively impacts PTC&amp;#8217;s market share. Consistent with the agreements between Ionis and Akcea, the companies will share all payments, including royalties.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;At the commencement of this collaboration, we identified two performance obligations, which were the licenses Akcea granted to PTC to commercialize TEGSEDI and WAYLIVRA in Latin America in the third quarter of 2018. Akcea recognized $12 million in license fee revenue at that time because PTC had full use of both licenses without any continuing involvement from Akcea. Akcea does not have any remaining performance obligations under its collaboration with PTC. Akcea can still earn additional payments and royalties as PTC commercializes the drugs.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Akcea is responsible for the 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 SG&amp;amp;A expense. For example, during the third quarter of 2018, we recognized $7.2 million of sublicense revenue in our Ionis Core operating segment results related to our portion of the PTC license fee Akcea paid us. In our consolidated results, we eliminate this sublicense revenue and expense. Any cash Akcea receives is included in our consolidated balance sheet.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with PTC (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12.0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12.0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;3&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Our condensed consolidated balance sheet at September 30, 2018 and December 31, 2017 did not include any deferred revenue related to our relationship with PTC.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:CollaborativeArrangementDisclosureTextBlock>
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  <us-gaap:CommonStockSharesAuthorized contextRef="c20171231" unitRef="U001" decimals="INF">300000000</us-gaap:CommonStockSharesAuthorized>
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We amended the credit agreement in February 2016 to increase the amount available for us to borrow. Under the amended credit agreement, we can borrow up to a maximum of $30 million of revolving credit for general working capital purposes. Under the credit agreement interest is payable monthly in arrears on the outstanding principal at a borrowing rate based on our option of:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 58.5pt; vertical-align: top; align: right;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 36pt;"&gt;(i)&lt;/div&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify;"&gt;a floating rate equal to the one-month London Interbank Offered Rate, or LIBOR, in effect plus 1.25 percent per annum;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 58.5pt; vertical-align: top; align: right;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 36pt;"&gt;(ii)&lt;/div&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify;"&gt;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&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 58.5pt; vertical-align: top; align: right;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 36pt;"&gt;(iii)&lt;/div&gt;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify;"&gt;a fixed rate equal to the LIBOR swap rate during the period of the loan.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Additionally, we pay 0.25 percent per annum, payable quarterly in arrears, for any amount unused under the credit facility. As of September 30, 2018 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.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The credit agreement includes customary affirmative and negative covenants and restrictions. We are in compliance with all covenants of the credit agreement.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Research and Development and Manufacturing Facilities&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;In July 2017, &lt;/font&gt;we purchased the building that houses our primary R&amp;amp;D facility and the building that houses our manufacturing facility for $79.4 million and $14.0 million, respectively. We financed the purchase of our primary R&amp;amp;D facility and our manufacturing facility, with mortgage debt of $51.3 million and $9.1 million, respectively. Our primary R&amp;amp;D facility mortgage has an interest rate of 3.88 percent. Our manufacturing facility 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.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:DebtAndCapitalLeasesDisclosuresTextBlock>
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  <us-gaap:DebtPolicyTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Convertible debt&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:DebtPolicyTextBlock>
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  <!--Interest rate-Convertible Senior Notes 2.75 Percent [Member]-->
  <us-gaap:DebtInstrumentInterestRateStatedPercentage contextRef="c20170930_DebtInstrumentAxis_ConvertibleSeniorNotes275PercentMember" unitRef="U003" decimals="INF">0.0275</us-gaap:DebtInstrumentInterestRateStatedPercentage>
  <!--Interest rate-Convertible Senior Notes 1 Percent [Member]-->
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  <!--Interest rate-Manufacturing Facility [Member]-->
  <us-gaap:DebtInstrumentInterestRateStatedPercentage contextRef="c20170731_PropertyPlantAndEquipmentByTypeAxis_ManufacturingFacilityMember" unitRef="U003" decimals="INF">0.042</us-gaap:DebtInstrumentInterestRateStatedPercentage>
  <!--Interest rate-Primary Research and Development Facility [Member]-->
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  <!--Maturity date-Fixed Rate Note with Morgan Stanley [Member]-->
  <us-gaap:DebtInstrumentMaturityDate contextRef="c20180101to20180930_DebtInstrumentAxis_FixedRateNoteWithMorganStanleyMember">2019-09-30</us-gaap:DebtInstrumentMaturityDate>
  <!--Depreciation-->
  <us-gaap:Depreciation contextRef="c20180101to20180930" unitRef="U002" decimals="-3">7650000</us-gaap:Depreciation>
  <!--Depreciation-->
  <us-gaap:Depreciation contextRef="c20170101to20170930" unitRef="U002" decimals="-3">6138000</us-gaap:Depreciation>
  <!--Basic net income (loss) per share (in dollars per share)-->
  <us-gaap:EarningsPerShareBasic contextRef="c20170101to20170930" unitRef="U004" decimals="2">0.13</us-gaap:EarningsPerShareBasic>
  <!--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)-->
  <us-gaap:EarningsPerShareBasic contextRef="c20180101to20180930" unitRef="U004" decimals="2">-0.33</us-gaap:EarningsPerShareBasic>
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  <!--Basic net income (loss) per share (in dollars per share)-Topic 606 Adjustment [Member]-Topic 606 [Member]-->
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  <!--Basic net income (loss) per share (in dollars per share)-Topic 606 Adjustment [Member]-Topic 606 [Member]-->
  <us-gaap:EarningsPerShareBasic contextRef="c20170101to20170930_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201409Member_InitialApplicationPeriodCumulativeEffectTransitionAxis_DifferenceBetweenRevenueGuidanceInEffectBeforeAndAfterTopic606Member" unitRef="U004" decimals="2">0.11</us-gaap:EarningsPerShareBasic>
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  <us-gaap:EarningsPerShareBasic contextRef="c20170101to20170930_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201409Member_InitialApplicationPeriodCumulativeEffectTransitionAxis_CalculatedUnderRevenueGuidanceInEffectBeforeTopic606Member" unitRef="U004" decimals="2">0.02</us-gaap:EarningsPerShareBasic>
  <!--Basic net income (loss) per share (in dollars per share)-Akcea Therapeutics, Inc. [Member]-Common Stock [Member]-->
  <us-gaap:EarningsPerShareBasic contextRef="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U004" decimals="2">-0.73</us-gaap:EarningsPerShareBasic>
  <!--Basic net income (loss) per share (in dollars per share)-Akcea Therapeutics, Inc. [Member]-Common Stock [Member]-->
  <us-gaap:EarningsPerShareBasic contextRef="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U004" decimals="2">-1.93</us-gaap:EarningsPerShareBasic>
  <!--Basic net income (loss) per share (in dollars per share)-Common Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:EarningsPerShareBasic contextRef="c20170101to20170930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U004" decimals="2">-3.12</us-gaap:EarningsPerShareBasic>
  <!--Basic net income (loss) per share (in dollars per share)-Common Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:EarningsPerShareBasic contextRef="c20170701to20170930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U004" decimals="2">-0.33</us-gaap:EarningsPerShareBasic>
  <!--Basic net income (loss) per share (in dollars per share)-Convertible Preferred Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:EarningsPerShareBasic contextRef="c20170701to20170930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_ConvertiblePreferredStockMember" unitRef="U004" decimals="2">-0.01</us-gaap:EarningsPerShareBasic>
  <!--Basic net income (loss) per share (in dollars per share)-Convertible Preferred Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:EarningsPerShareBasic contextRef="c20170101to20170930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_ConvertiblePreferredStockMember" unitRef="U004" decimals="2">-2.16</us-gaap:EarningsPerShareBasic>
  <!--Earnings Per Share, Policy [Policy Text Block]-->
  <us-gaap:EarningsPerSharePolicyTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Basic and diluted net income (loss) per share&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Basic net income (loss) per share&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The calculation of total net income (loss) attributable to our common stockholders for the three and nine months ended September 30, 2018 and 2017 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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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; color: #000000;"&gt;September 30, 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 align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Three months ended September 30, 2018&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Weighted&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Average Shares&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Net Income (Loss)&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis&amp;#8217; Portion of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s Net Loss&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;65,538&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.73&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(47,843&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Akcea&amp;#8217;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(47,843&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Ionis&amp;#8217; stand-alone net income&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;43,226&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(4,616&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;143,314&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.03&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Akcea&amp;#8217;s net loss per share calculation for the nine months ended &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;September 30, 2018 included two components: (1) Akcea&amp;#8217;s net loss from its statement of operations and (2) deemed distributions related to the license of &lt;/font&gt;TEGSEDI in the second quarter of 2018. Because we own more than 50 percent of Akcea, we and Akcea are under common control.&amp;#160;As such, Akcea accounted for the TEGSEDI transaction using common control guidance.&amp;#160;Accordingly, Akcea recorded the license we granted to them at carrying value.&amp;#160;In addition, Akcea recorded the consideration it paid to us in excess of the carrying value as a deemed distribution.&amp;#160;Accounting rules required Akcea to include these deemed distributions in their net loss per share calculation as if Akcea had paid us a dividend. &amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Our basic net loss per share for the &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;nine months ended September 30, 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 align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Nine months ended September 30, 2018&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Weighted&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Average Shares&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Net Loss&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis&amp;#8217; Portion of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s Net Loss&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;57,347&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1.93&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(110,680&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Akcea&amp;#8217;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(110,680&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Ionis&amp;#8217; stand-alone net income&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;67,517&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(43,162&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;132,518&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.33&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Prior to Akcea&amp;#8217;s IPO in July 2017, we owned Akcea series A convertible preferred stock, which included a six percent cumulative dividend. Upon completion of Akcea&amp;#8217;s IPO in July 2017, our preferred stock was converted into common stock on a 1:1 basis. The preferred stock dividend was not paid at the IPO because the IPO was not a liquidation event or a change in control. During the three and nine months ended September 30, 2017, Akcea used a two-class method to compute its net income (loss) per share because it had both common and preferred shares outstanding during the periods. The two-class method required Akcea to calculate its net income (loss) per share&amp;#160;for each class of stock by dividing total distributable losses applicable to preferred and common stock, including the&amp;#160;six percent&amp;#160;cumulative dividend contractually due to series A convertible preferred shareholders, by the weighted-average of preferred and common shares outstanding during the requisite period. Since Akcea used the two-class method, accounting rules required us to include our portion of Akcea's net income (loss) per share for both Akcea's common and preferred shares that we owned in our calculation of basic and diluted net income (loss) per share for three and nine months ended September 30, 2017.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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; color: #000000;"&gt;September 30, 2017&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 align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Three months ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Weighted&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Average Shares&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Net Loss&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis&amp;#8217; Portion of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s Net Loss&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;36,556&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.33&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(12,063&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Preferred shares&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5,651&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.01&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(57&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Akcea&amp;#8217;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(12,120&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Ionis&amp;#8217; stand-alone net income&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;10,144&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,976&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;124,370&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.02&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Our basic net income per share for the &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;nine months ended September 30, 2017&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 align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Nine months ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Weighted&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Average Shares&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Net Loss&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis&amp;#8217; Portion of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s Net Loss&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12,319&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(3.12&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(38,435&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Preferred shares&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;21,055&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2.16&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(45,479&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Akcea&amp;#8217;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(83,914&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Ionis&amp;#8217; stand-alone net income&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;100,235&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16,321&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;123,746&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.13&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Dilutive net income (loss per share)&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;For the three and nine months ended September 30, 2018 and for the three months ended September 30, 2017, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1 percent convertible senior notes;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;2&amp;#190; percent convertible senior notes;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Dilutive stock options;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Unvested restricted stock units; and&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Employee Stock Purchase Plan, or ESPP.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;For the nine months ended September 30, 2017, 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 those periods. Diluted common equivalent shares for the nine months ended September 30, 2017 consisted of the following (in thousands except per share amounts):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Nine months ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Income&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Shares&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Per-Share&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Amount&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16,321&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;123,746&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.13&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -8.9pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,658&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: 0.1pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;430&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; text-indent: 9.1pt;"&gt;Shares issuable related to our ESPP&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;24&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Income available to Ionis common stockholders, plus assumed conversions&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16,321&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;125,858&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.13&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;For the nine months ended September 30, 2017, the calculation excluded the 1 percent and 2&amp;#190; 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;</us-gaap:EarningsPerSharePolicyTextBlock>
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  <us-gaap:EarningsPerShareDiluted contextRef="c20170101to20170930" unitRef="U004" decimals="2">0.13</us-gaap:EarningsPerShareDiluted>
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  <us-gaap:EarningsPerShareDiluted contextRef="c20180701to20180930" unitRef="U004" decimals="2">-0.03</us-gaap:EarningsPerShareDiluted>
  <!--Diluted net income (loss) per share (in dollars per share)-->
  <us-gaap:EarningsPerShareDiluted contextRef="c20180101to20180930" unitRef="U004" decimals="2">-0.33</us-gaap:EarningsPerShareDiluted>
  <!--Diluted net income (loss) per share (in dollars per share)-->
  <us-gaap:EarningsPerShareDiluted contextRef="c20170701to20170930" unitRef="U004" decimals="2">-0.02</us-gaap:EarningsPerShareDiluted>
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  <!--Employee-related Liabilities, Current-->
  <us-gaap:EmployeeRelatedLiabilitiesCurrent contextRef="c20180930" unitRef="U002" decimals="-3">24259000</us-gaap:EmployeeRelatedLiabilitiesCurrent>
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  <!--Fair Value, Measurement with Unobservable Inputs Reconciliation, Recurring Basis, Asset Transfers Into Level 3-Potential Future Premium [Member]-->
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  <!--Fair Value Disclosures [Text Block]-->
  <us-gaap:FairValueDisclosuresTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;4.&amp;#160; Fair Value Measurements&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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. During the nine months ended September 30, 2018, there were no transfers between our Level 1 and Level 2 investments. When we recognize transfers between levels of the fair value hierarchy, we recognize the transfer on the date the event or change in circumstances that caused the transfer occurs.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following tables present the major security types we held at September 30, 2018 and December 31, 2017 that are regularly measured and carried at fair value. At September 30, 2018 and December 31, 2017, we did not have any financial instruments that we valued using Level 3 inputs. 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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;At&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30, 2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Quoted Prices in&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Active Markets&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;(Level 1)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Significant Other&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;395,649&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;395,649&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Corporate debt securities (2)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,078,960&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,078,960&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by U.S. government agencies (3)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;175,167&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;175,167&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by the U.S. Treasury (3)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;164,053&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;164,053&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (3)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;80,658&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;80,658&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,894,487&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;559,702&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,334,785&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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 align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;At&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;December 31, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Quoted Prices in&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Active Markets&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;(Level 1)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Significant Other&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;86,262&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;86,262&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Corporate debt securities (3)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;647,461&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;647,461&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by U.S. government agencies (3)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;136,325&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;136,325&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by the U.S. Treasury (3)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;30,818&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;30,818&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (4)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;93,932&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;93,932&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr style="height: 16px;"&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;994,798&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;117,080&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;877,718&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;(1)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Included in cash and cash equivalents on our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;(2)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;At September 30, 2018, $19.7 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;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;(3)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Included in short-term investments on our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;(4)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;At December 31, 2017, $3.5 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;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Other Fair Value Disclosures&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Novartis Future Stock Purchase&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In January 2017, we and Akcea entered into a SPA with Novartis. As part of the SPA, Novartis was required to purchase $50 million of Akcea&amp;#8217;s common stock at the IPO price or our common stock at a premium if an IPO did not occur by April 2018. Therefore, at the inception of the SPA, we recorded a $5.0 million asset representing the fair value of the potential future premium we could have received if Novartis purchased our common stock. We determined the fair value of the future premium by calculating the value based on the stated premium in the SPA and estimating the probability of an Akcea IPO. We also included a &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;lack of marketability discount when we determined the fair value of the premium because we would have issued unregistered shares to Novartis if they had purchased our common stock. We measured this asset using Level 3 inputs and recorded it in other assets on our consolidated balance sheet. Because Akcea completed its IPO before April 2018, Novartis did not purchase additional shares of Ionis stock. Therefore, we wrote-off the remaining balance to other expenses in the third quarter of 2017 because this asset no longer had any value.&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following is a reconciliation of the potential premium we would have received if Akcea had not completed its IPO, measured at fair value on a recurring basis using significant unobservable inputs (Level 3) for the nine months ended September 30, 2017 (in thousands):&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 88%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; margin-left: 9pt; text-indent: -9pt;"&gt;Beginning balance of Level 3 instruments at January 1, 2017&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 88%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; margin-left: 9pt; text-indent: -9pt;"&gt;Value of the potential premium we would have received from Novartis at inception of the SPA (January 2017)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5,035&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 88%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; margin-left: 9pt; text-indent: -9pt;"&gt;Recurring fair value adjustment during the nine months ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(5,035&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 88%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; margin-left: 9pt; text-indent: -9pt;"&gt;Ending balance of Level 3 instruments at September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; margin-left: 36pt;"&gt;Convertible Notes&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Our 1 percent notes had a fair value of $725.7 million at September 30, 2018. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.&lt;/div&gt;&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="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following tables present the major security types we held at September 30, 2018 and December 31, 2017 that are regularly measured and carried at fair value. At September 30, 2018 and December 31, 2017, we did not have any financial instruments that we valued using Level 3 inputs. 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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;At&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30, 2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Quoted Prices in&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Active Markets&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;(Level 1)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Significant Other&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;395,649&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;395,649&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Corporate debt securities (2)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,078,960&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,078,960&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by U.S. government agencies (3)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;175,167&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;175,167&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by the U.S. Treasury (3)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;164,053&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;164,053&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (3)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;80,658&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;80,658&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,894,487&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;559,702&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,334,785&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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 align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;At&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;December 31, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Quoted Prices in&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Active Markets&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;(Level 1)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Significant Other&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;86,262&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;86,262&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Corporate debt securities (3)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;647,461&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;647,461&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by U.S. government agencies (3)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;136,325&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;136,325&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by the U.S. Treasury (3)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;30,818&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;30,818&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (4)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;93,932&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;93,932&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr style="height: 16px;"&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;994,798&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;117,080&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;877,718&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;(1)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Included in cash and cash equivalents on our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;(2)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;At September 30, 2018, $19.7 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;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;(3)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Included in short-term investments on our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;(4)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;At December 31, 2017, $3.5 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;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock>
  <!--Fair Value, Assets Measured on Recurring Basis, Unobservable Input Reconciliation [Table Text Block]-->
  <us-gaap:FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationTextBlock contextRef="c20180101to20180930">&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following is a reconciliation of the potential premium we would have received if Akcea had not completed its IPO, measured at fair value on a recurring basis using significant unobservable inputs (Level 3) for the nine months ended September 30, 2017 (in thousands):&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 88%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; margin-left: 9pt; text-indent: -9pt;"&gt;Beginning balance of Level 3 instruments at January 1, 2017&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 88%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; margin-left: 9pt; text-indent: -9pt;"&gt;Value of the potential premium we would have received from Novartis at inception of the SPA (January 2017)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5,035&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 88%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; margin-left: 9pt; text-indent: -9pt;"&gt;Recurring fair value adjustment during the nine months ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(5,035&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 88%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; margin-left: 9pt; text-indent: -9pt;"&gt;Ending balance of Level 3 instruments at September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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:FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationTextBlock>
  <!--Fair Value, Measurement with Unobservable Inputs Reconciliation, Recurring Basis, Asset Value-Potential Future Premium [Member]-->
  <us-gaap:FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetValue contextRef="c20161231_FairValueByAssetClassAxis_PotentialFuturePremiumMember" unitRef="U002" decimals="-3">0</us-gaap:FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetValue>
  <!--Fair Value, Measurement with Unobservable Inputs Reconciliation, Recurring Basis, Asset Value-Potential Future Premium [Member]-->
  <us-gaap:FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetValue contextRef="c20170930_FairValueByAssetClassAxis_PotentialFuturePremiumMember" unitRef="U002" decimals="-3">0</us-gaap:FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetValue>
  <!--Finite-Lived Intangible Assets, Net-->
  <us-gaap:FiniteLivedIntangibleAssetsNet contextRef="c20171231" unitRef="U002" decimals="-3">22004000</us-gaap:FiniteLivedIntangibleAssetsNet>
  <!--Finite-Lived Intangible Assets, Net-->
  <us-gaap:FiniteLivedIntangibleAssetsNet contextRef="c20180930" unitRef="U002" decimals="-3">24027000</us-gaap:FiniteLivedIntangibleAssetsNet>
  <!--Impairment or Disposal of Long-Lived Assets, Including Intangible Assets, Policy [Policy Text Block]-->
  <us-gaap:ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Long-lived assets&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We evaluate long-lived assets, which include property, plant and equipment 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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock>
  <!--Income (Loss) from Continuing Operations before Equity Method Investments, Income Taxes, Noncontrolling Interest-->
  <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments contextRef="c20170701to20170930" unitRef="U002" decimals="-3">-6532000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments>
  <!--Income (Loss) from Continuing Operations before Equity Method Investments, Income Taxes, Noncontrolling Interest-->
  <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments contextRef="c20170101to20170930" unitRef="U002" decimals="-3">-432000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments>
  <!--Income (Loss) from Continuing Operations before Equity Method Investments, Income Taxes, Noncontrolling Interest-->
  <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments contextRef="c20180701to20180930" unitRef="U002" decimals="-3">-19913000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments>
  <!--Income (Loss) from Continuing Operations before Equity Method Investments, Income Taxes, Noncontrolling Interest-->
  <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments contextRef="c20180101to20180930" unitRef="U002" decimals="-3">-86923000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments>
  <!--Income Tax Expense (Benefit)-->
  <us-gaap:IncomeTaxExpenseBenefit contextRef="c20170701to20170930" unitRef="U002" decimals="-3">961000</us-gaap:IncomeTaxExpenseBenefit>
  <!--Income Tax Expense (Benefit)-->
  <us-gaap:IncomeTaxExpenseBenefit contextRef="c20180701to20180930" unitRef="U002" decimals="-3">452000</us-gaap:IncomeTaxExpenseBenefit>
  <!--Income Tax Expense (Benefit)-->
  <us-gaap:IncomeTaxExpenseBenefit contextRef="c20170101to20170930" unitRef="U002" decimals="-3">1184000</us-gaap:IncomeTaxExpenseBenefit>
  <!--Income Tax Expense (Benefit)-->
  <us-gaap:IncomeTaxExpenseBenefit contextRef="c20180101to20180930" unitRef="U002" decimals="-3">824000</us-gaap:IncomeTaxExpenseBenefit>
  <!--Increase (Decrease) in Contract with Customer, Liability-->
  <us-gaap:IncreaseDecreaseInContractWithCustomerLiability contextRef="c20180101to20180930" unitRef="U002" decimals="-3">447168000</us-gaap:IncreaseDecreaseInContractWithCustomerLiability>
  <!--Increase (Decrease) in Contract with Customer, Liability-->
  <us-gaap:IncreaseDecreaseInContractWithCustomerLiability contextRef="c20170101to20170930" unitRef="U002" decimals="-3">31071000</us-gaap:IncreaseDecreaseInContractWithCustomerLiability>
  <!--Increase (Decrease) in Contract with Customer, Liability-As Previously Reported Under Topic 605 [Member]-Topic 606 [Member]-->
  <us-gaap:IncreaseDecreaseInContractWithCustomerLiability contextRef="c20170101to20170930_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201409Member_InitialApplicationPeriodCumulativeEffectTransitionAxis_CalculatedUnderRevenueGuidanceInEffectBeforeTopic606Member" unitRef="U002" decimals="-3">42091000</us-gaap:IncreaseDecreaseInContractWithCustomerLiability>
  <!--Increase (Decrease) in Contract with Customer, Liability-Topic 606 Adjustment [Member]-Topic 606 [Member]-->
  <us-gaap:IncreaseDecreaseInContractWithCustomerLiability contextRef="c20170101to20170930_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201409Member_InitialApplicationPeriodCumulativeEffectTransitionAxis_DifferenceBetweenRevenueGuidanceInEffectBeforeAndAfterTopic606Member" unitRef="U002" decimals="-3">-11020000</us-gaap:IncreaseDecreaseInContractWithCustomerLiability>
  <!--Increase (Decrease) in Contract with Customer, Asset-->
  <us-gaap:IncreaseDecreaseInContractWithCustomerAsset contextRef="c20170101to20170930" unitRef="U002" decimals="-3">-65119000</us-gaap:IncreaseDecreaseInContractWithCustomerAsset>
  <!--Increase (Decrease) in Contract with Customer, Asset-->
  <us-gaap:IncreaseDecreaseInContractWithCustomerAsset contextRef="c20180101to20180930" unitRef="U002" decimals="-3">-48223000</us-gaap:IncreaseDecreaseInContractWithCustomerAsset>
  <!--Increase (Decrease) in Accounts Payable-->
  <us-gaap:IncreaseDecreaseInAccountsPayable contextRef="c20170101to20170930" unitRef="U002" decimals="-3">-1707000</us-gaap:IncreaseDecreaseInAccountsPayable>
  <!--Increase (Decrease) in Accounts Payable-->
  <us-gaap:IncreaseDecreaseInAccountsPayable contextRef="c20180101to20180930" unitRef="U002" decimals="-3">-13606000</us-gaap:IncreaseDecreaseInAccountsPayable>
  <!--Increase (Decrease) in Inventories-->
  <us-gaap:IncreaseDecreaseInInventories contextRef="c20170101to20170930" unitRef="U002" decimals="-3">962000</us-gaap:IncreaseDecreaseInInventories>
  <!--Increase (Decrease) in Inventories-->
  <us-gaap:IncreaseDecreaseInInventories contextRef="c20180101to20180930" unitRef="U002" decimals="-3">-1604000</us-gaap:IncreaseDecreaseInInventories>
  <!--Increase (Decrease) in Other Operating Assets-->
  <us-gaap:IncreaseDecreaseInOtherOperatingAssets contextRef="c20170101to20170930" unitRef="U002" decimals="-3">34866000</us-gaap:IncreaseDecreaseInOtherOperatingAssets>
  <!--Increase (Decrease) in Other Operating Assets-->
  <us-gaap:IncreaseDecreaseInOtherOperatingAssets contextRef="c20180101to20180930" unitRef="U002" decimals="-3">26573000</us-gaap:IncreaseDecreaseInOtherOperatingAssets>
  <!--Increase (Decrease) in Other Employee-Related Liabilities-->
  <us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities contextRef="c20180101to20180930" unitRef="U002" decimals="-3">-892000</us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities>
  <!--Increase (Decrease) in Other Employee-Related Liabilities-->
  <us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities contextRef="c20170101to20170930" unitRef="U002" decimals="-3">-8999000</us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities>
  <!--Shares issuable related to stock-based compensation (in shares)-Restricted Stock [Member]-->
  <us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements contextRef="c20170101to20170930_AwardTypeAxis_RestrictedStockMember" unitRef="U001" decimals="-3">430000</us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements>
  <!--Shares issuable related to stock-based compensation (in shares)-Employee Stock Option [Member]-->
  <us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements contextRef="c20170101to20170930_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U001" decimals="-3">1658000</us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements>
  <!--Intangible Assets, Finite-Lived, Policy [Policy Text Block]-->
  <us-gaap:IntangibleAssetsFiniteLivedPolicy contextRef="c20180101to20180930">&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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="c20180101to20180930" unitRef="U002" decimals="-3">33332000</us-gaap:InterestExpense>
  <!--Interest Expense-->
  <us-gaap:InterestExpense contextRef="c20180701to20180930" unitRef="U002" decimals="-3">11282000</us-gaap:InterestExpense>
  <!--Interest Expense-->
  <us-gaap:InterestExpense contextRef="c20170101to20170930" unitRef="U002" decimals="-3">33966000</us-gaap:InterestExpense>
  <!--Interest Expense-->
  <us-gaap:InterestExpense contextRef="c20170701to20170930" unitRef="U002" decimals="-3">10825000</us-gaap:InterestExpense>
  <!--Interest Paid, Excluding Capitalized Interest, Operating Activities-->
  <us-gaap:InterestPaidNet contextRef="c20170101to20170930" unitRef="U002" decimals="-3">4020000</us-gaap:InterestPaidNet>
  <!--Interest Paid, Excluding Capitalized Interest, Operating Activities-->
  <us-gaap:InterestPaidNet contextRef="c20180101to20180930" unitRef="U002" decimals="-3">5434000</us-gaap:InterestPaidNet>
  <!--Inventory Write-down-->
  <us-gaap:InventoryWriteDown contextRef="c20180101to20180930" unitRef="U002" decimals="-3">0</us-gaap:InventoryWriteDown>
  <!--Inventory Write-down-->
  <us-gaap:InventoryWriteDown contextRef="c20170101to20170930" unitRef="U002" decimals="-3">0</us-gaap:InventoryWriteDown>
  <!--Inventory, Net-->
  <us-gaap:InventoryNet contextRef="c20180930" unitRef="U002" decimals="-3">8378000</us-gaap:InventoryNet>
  <!--Inventory, Net-->
  <us-gaap:InventoryNet contextRef="c20171231" unitRef="U002" decimals="-3">9982000</us-gaap:InventoryNet>
  <!--Inventory, Policy [Policy Text Block]-->
  <us-gaap:InventoryPolicyTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Inventory valuation&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;We reflect our inventory on our 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 drugs because until we use these raw materials they have alternative future uses. We include in inventory raw material costs for drugs 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 drug. For example, if one of our drugs failed, we could use the raw materials for that drug to manufacture our other drugs. We expense these costs as R&amp;amp;D expenses when we begin to manufacture API for a particular drug if the drug has not been approved for marketing by a regulatory agency.&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;We obtained the first regulatory approval for TEGSEDI in July 2018. At September 30, 2018 and December 31, 2017, 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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 drugs and historical write-offs. We did not record any inventory write-offs for the nine months ended September 30, 2018 and 2017.&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="c20170101to20170930" unitRef="U002" decimals="-3">7504000</us-gaap:InvestmentIncomeNet>
  <!--Investment Income, Net-->
  <us-gaap:InvestmentIncomeNet contextRef="c20180701to20180930" unitRef="U002" decimals="-3">9963000</us-gaap:InvestmentIncomeNet>
  <!--Investment Income, Net-->
  <us-gaap:InvestmentIncomeNet contextRef="c20170701to20170930" unitRef="U002" decimals="-3">2811000</us-gaap:InvestmentIncomeNet>
  <!--Investment Income, Net-->
  <us-gaap:InvestmentIncomeNet contextRef="c20180101to20180930" unitRef="U002" decimals="-3">18711000</us-gaap:InvestmentIncomeNet>
  <!--Investments Classified by Contractual Maturity Date [Table Text Block]-->
  <us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following table summarizes the contract maturity of the available-for-sale securities we held as of September 30, 2018:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 60%; border-collapse: collapse;"&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 46.8pt; text-indent: -9pt;"&gt;One year or less&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;80%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 46.8pt; text-indent: -9pt;"&gt;After one year but within two years&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;15%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 46.8pt; text-indent: -9pt;"&gt;After two years but within three years&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; border-bottom: #000000 2px solid; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;5%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 83.04%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 46.8pt; text-indent: -9pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 16.96%; vertical-align: bottom; border-bottom: #000000 4px double; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;100%&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>
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  <us-gaap:Liabilities contextRef="c20180930" unitRef="U002" decimals="-3">1407769000</us-gaap:Liabilities>
  <!--Liabilities-->
  <us-gaap:Liabilities contextRef="c20171231" unitRef="U002" decimals="-3">957494000</us-gaap:Liabilities>
  <!--Liabilities and Equity-->
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  <!--Liabilities and Equity-->
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  <!--Liabilities, Current-->
  <us-gaap:LiabilitiesCurrent contextRef="c20171231" unitRef="U002" decimals="-3">243612000</us-gaap:LiabilitiesCurrent>
  <!--Liabilities, Current-->
  <us-gaap:LiabilitiesCurrent contextRef="c20180930" unitRef="U002" decimals="-3">260238000</us-gaap:LiabilitiesCurrent>
  <!--Commitment fee percentage on unused capacity-Morgan Stanley Private Bank, National Association [Member]-Revolving Line of Credit [Member]-->
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  <!--Outstanding borrowings-Fixed Rate Note with Morgan Stanley [Member]-->
  <us-gaap:LineOfCredit contextRef="c20180930_DebtInstrumentAxis_FixedRateNoteWithMorganStanleyMember" unitRef="U002" decimals="-5">12500000</us-gaap:LineOfCredit>
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  <!--Long-term mortgage debt-->
  <us-gaap:LongTermLoansFromBank contextRef="c20180930" unitRef="U002" decimals="-3">59825000</us-gaap:LongTermLoansFromBank>
  <!--Long-term mortgage debt-->
  <us-gaap:LongTermLoansFromBank contextRef="c20171231" unitRef="U002" decimals="-3">59771000</us-gaap:LongTermLoansFromBank>
  <!--Noncontrolling interest in Akcea Therapeutics, Inc.-->
  <us-gaap:MinorityInterest contextRef="c20180930" unitRef="U002" decimals="-3">129594000</us-gaap:MinorityInterest>
  <!--Noncontrolling interest in Akcea Therapeutics, Inc.-->
  <us-gaap:MinorityInterest contextRef="c20171231" unitRef="U002" decimals="-3">84267000</us-gaap:MinorityInterest>
  <!--Noncontrolling interest in Akcea Therapeutics, Inc.-Topic 606 [Member]-Topic 606 Adjustment [Member]-->
  <us-gaap:MinorityInterest contextRef="c20171231_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201409Member_InitialApplicationPeriodCumulativeEffectTransitionAxis_DifferenceBetweenRevenueGuidanceInEffectBeforeAndAfterTopic606Member" unitRef="U002" decimals="-3">-3580000</us-gaap:MinorityInterest>
  <!--Noncontrolling interest in Akcea Therapeutics, Inc.-As Previously Reported Under Topic 605 [Member]-Topic 606 [Member]-->
  <us-gaap:MinorityInterest contextRef="c20171231_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201409Member_InitialApplicationPeriodCumulativeEffectTransitionAxis_CalculatedUnderRevenueGuidanceInEffectBeforeTopic606Member" unitRef="U002" decimals="-3">87847000</us-gaap:MinorityInterest>
  <!--Noncontrolling Interest, Ownership Percentage by Parent-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:MinorityInterestOwnershipPercentageByParent contextRef="c20180930_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2">0.75</us-gaap:MinorityInterestOwnershipPercentageByParent>
  <!--Noncontrolling Interest, Ownership Percentage by Parent-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:MinorityInterestOwnershipPercentageByParent contextRef="c20170731_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2">0.68</us-gaap:MinorityInterestOwnershipPercentageByParent>
  <!--Noncontrolling Interest, Ownership Percentage by Parent-Akcea Therapeutics, Inc. [Member]-Subsequent Event [Member]-->
  <us-gaap:MinorityInterestOwnershipPercentageByParent contextRef="c20181031_OwnershipAxis_AkceaTherapeuticsIncMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2">0.76</us-gaap:MinorityInterestOwnershipPercentageByParent>
  <!--Noncontrolling Interest, Ownership Percentage by Parent-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:MinorityInterestOwnershipPercentageByParent contextRef="c20180331_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2">0.68</us-gaap:MinorityInterestOwnershipPercentageByParent>
  <!--Noncontrolling Interest, Ownership Percentage by Parent-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:MinorityInterestOwnershipPercentageByParent contextRef="c20180430_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2">0.75</us-gaap:MinorityInterestOwnershipPercentageByParent>
  <!--Net Cash Provided by (Used in) Financing Activities-->
  <us-gaap:NetCashProvidedByUsedInFinancingActivities contextRef="c20170101to20170930" unitRef="U002" decimals="-3">224830000</us-gaap:NetCashProvidedByUsedInFinancingActivities>
  <!--Net Cash Provided by (Used in) Financing Activities-->
  <us-gaap:NetCashProvidedByUsedInFinancingActivities contextRef="c20180101to20180930" unitRef="U002" decimals="-3">466219000</us-gaap:NetCashProvidedByUsedInFinancingActivities>
  <!--Net Income (Loss) Available to Common Stockholders, Diluted-->
  <us-gaap:NetIncomeLossAvailableToCommonStockholdersDiluted contextRef="c20170101to20170930" unitRef="U002" decimals="-3">16321000</us-gaap:NetIncomeLossAvailableToCommonStockholdersDiluted>
  <!--Net Cash Provided by (Used in) Investing Activities-->
  <us-gaap:NetCashProvidedByUsedInInvestingActivities contextRef="c20170101to20170930" unitRef="U002" decimals="-3">-304079000</us-gaap:NetCashProvidedByUsedInInvestingActivities>
  <!--Net Cash Provided by (Used in) Investing Activities-->
  <us-gaap:NetCashProvidedByUsedInInvestingActivities contextRef="c20180101to20180930" unitRef="U002" decimals="-3">-603356000</us-gaap:NetCashProvidedByUsedInInvestingActivities>
  <!--Net income (loss) available to Ionis common shareholders-->
  <us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic contextRef="c20180701to20180930" unitRef="U002" decimals="-3">-4616000</us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic>
  <!--Net income (loss) available to Ionis common shareholders-->
  <us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic contextRef="c20170101to20170930" unitRef="U002" decimals="-3">16321000</us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic>
  <!--Net income (loss) available to Ionis common shareholders-->
  <us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic contextRef="c20180101to20180930" unitRef="U002" decimals="-3">-43162000</us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic>
  <!--Net income (loss) available to Ionis common shareholders-->
  <us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic contextRef="c20170701to20170930" unitRef="U002" decimals="-3">-1976000</us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic>
  <!--Net Income (Loss) Attributable to Noncontrolling Interest-->
  <us-gaap:NetIncomeLossAttributableToNoncontrollingInterest contextRef="c20170701to20170930" unitRef="U002" decimals="-3">-4882000</us-gaap:NetIncomeLossAttributableToNoncontrollingInterest>
  <!--Net Income (Loss) Attributable to Noncontrolling Interest-->
  <us-gaap:NetIncomeLossAttributableToNoncontrollingInterest contextRef="c20180701to20180930" unitRef="U002" decimals="-3">-15806000</us-gaap:NetIncomeLossAttributableToNoncontrollingInterest>
  <!--Net Income (Loss) Attributable to Noncontrolling Interest-->
  <us-gaap:NetIncomeLossAttributableToNoncontrollingInterest contextRef="c20180101to20180930" unitRef="U002" decimals="-3">-41412000</us-gaap:NetIncomeLossAttributableToNoncontrollingInterest>
  <!--Net Income (Loss) Attributable to Noncontrolling Interest-->
  <us-gaap:NetIncomeLossAttributableToNoncontrollingInterest contextRef="c20170101to20170930" unitRef="U002" decimals="-3">-4882000</us-gaap:NetIncomeLossAttributableToNoncontrollingInterest>
  <!--Net Cash Provided by (Used in) Operating Activities-->
  <us-gaap:NetCashProvidedByUsedInOperatingActivities contextRef="c20180101to20180930" unitRef="U002" decimals="-3">487398000</us-gaap:NetCashProvidedByUsedInOperatingActivities>
  <!--Net Cash Provided by (Used in) Operating Activities-->
  <us-gaap:NetCashProvidedByUsedInOperatingActivities contextRef="c20170101to20170930" unitRef="U002" decimals="-3">153748000</us-gaap:NetCashProvidedByUsedInOperatingActivities>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-->
  <us-gaap:NetIncomeLoss contextRef="c20170701to20170930" unitRef="U002" decimals="-3">-2611000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-->
  <us-gaap:NetIncomeLoss contextRef="c20180101to20180930" unitRef="U002" decimals="-3">-46335000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-->
  <us-gaap:NetIncomeLoss contextRef="c20170101to20170930" unitRef="U002" decimals="-3">3266000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-->
  <us-gaap:NetIncomeLoss contextRef="c20180701to20180930" unitRef="U002" decimals="-3">-4559000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Topic 606 Adjustment [Member]-Topic 606 [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20170101to20170930_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201409Member_InitialApplicationPeriodCumulativeEffectTransitionAxis_DifferenceBetweenRevenueGuidanceInEffectBeforeAndAfterTopic606Member" unitRef="U002" decimals="-3">11982000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-As Previously Reported Under Topic 605 [Member]-Topic 606 [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20170101to20170930_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201409Member_InitialApplicationPeriodCumulativeEffectTransitionAxis_CalculatedUnderRevenueGuidanceInEffectBeforeTopic606Member" unitRef="U002" decimals="-3">-8716000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Topic 606 Adjustment [Member]-Topic 606 [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20170701to20170930_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201409Member_InitialApplicationPeriodCumulativeEffectTransitionAxis_DifferenceBetweenRevenueGuidanceInEffectBeforeAndAfterTopic606Member" unitRef="U002" decimals="-3">-1635000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Topic 606 [Member]-As Previously Reported Under Topic 605 [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20170701to20170930_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201409Member_InitialApplicationPeriodCumulativeEffectTransitionAxis_CalculatedUnderRevenueGuidanceInEffectBeforeTopic606Member" unitRef="U002" decimals="-3">-976000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Akcea Therapeutics, Inc. [Member]-Common Stock [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-3">-47843000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Ionis Core [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20180101to20180930_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3">67517000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Akcea Therapeutics, Inc. [Member]-Common Stock [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-3">-110680000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Ionis Core [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20180701to20180930_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3">43226000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U002" decimals="-3">-110680000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U002" decimals="-3">-47843000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Common Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20170101to20170930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-3">-38435000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Convertible Preferred Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20170701to20170930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_ConvertiblePreferredStockMember" unitRef="U002" decimals="-3">-57000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Convertible Preferred Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20170101to20170930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_ConvertiblePreferredStockMember" unitRef="U002" decimals="-3">-45479000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Ionis Core [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20170101to20170930_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3">100235000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20170101to20170930_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U002" decimals="-3">-83914000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20170701to20170930_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U002" decimals="-3">-12120000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Ionis Core [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20170701to20170930_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3">10144000</us-gaap:NetIncomeLoss>
  <!--Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders-Common Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
  <us-gaap:NetIncomeLoss contextRef="c20170701to20170930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-3">-12063000</us-gaap:NetIncomeLoss>
  <!--Cumulative effect of adoption on retained earnings-Topic 606 [Member]-->
  <us-gaap:NewAccountingPronouncementOrChangeInAccountingPrincipleCumulativeEffectOfChangeOnEquityOrNetAssets1 contextRef="c20171231_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201409Member" unitRef="U002" decimals="-5">-53600000</us-gaap:NewAccountingPronouncementOrChangeInAccountingPrincipleCumulativeEffectOfChangeOnEquityOrNetAssets1>
  <!--New Accounting Pronouncements, Policy [Policy Text Block]-->
  <us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left; text-indent: 36pt;"&gt;Impact of recently issued accounting standards&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In February 2016, the FASB issued amended accounting guidance related to lease accounting, which will require us to record all leases with a term longer than one year on our balance sheet. When we record leases on our balance sheet under the new guidance, we will record a liability with a value equal to the present value of payments we will make over the life of the lease and an asset representing the underlying leased asset. The new accounting guidance requires us to determine if our leases are operating or financing leases. We will record expense for operating leases on a straight-line basis as an operating expense. If we determine a lease is a financing&amp;#160;lease, we will record both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. The new lease standard is effective for annual and interim periods beginning after December 15, 2018, with early adoption permitted. We will adopt this guidance on January 1, 2019. We can choose from two methods of adoption. The first method requires us to reflect our leases on our balance sheet in the earliest comparative period presented in our financial statements. The second method requires us to reflect the impact of adoption on the date we adopt the new guidance and recognize a cumulative-effect adjustment to the opening balance of our accumulated deficit in that period. We are currently determining the method we will use to adopt the new guidance and assessing the effects the new guidance will have on our consolidated financial statements and disclosures.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 consolidated financial statements and disclosures.&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In December 2017, the SEC staff issued guidance to address how companies should account for the Tax Act of 2017, or the Tax Act, when an entity does not have the necessary information to complete the accounting for the Tax Act and gives entities up to one year from the enactment of the Tax Act to finalize their amounts. We recognized provisional amounts in our 2017 financial statements and in these financial statements. The ultimate impact may differ materially from these provisional amounts due to, among other things, additional analysis, changes in our interpretations and assumptions, additional regulatory guidance that may be issued, and other actions we may take resulting from the Tax Act. We will assess and update our provisional amounts and disclosures, as necessary, at year end 2018.&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In February 2018, the FASB issued updated guidance for reclassification of tax effects from accumulated other comprehensive income (loss). The updated guidance gives entities an option to reclassify amounts included in accumulated other comprehensive income (loss) that under the Tax Act do not have a way to be relieved, and allows a one-time reclassification to retained earnings. The updated guidance is effective for all entities for fiscal years beginning after December 31, 2018, and interim periods within those fiscal years. Early adoption is permitted, and adoption is optional. We are currently assessing the effects this updated guidance could have on our consolidated financial statements and timing of potential adoption.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In June 2018, the FASB issued updated guidance to simplify the accounting for stock-based compensation expense for nonemployees. Specifically, we are now expensing grants to nonemployees in a similar manner as grants to employees and our Board of Directors. Previously, we had to re-value these grants at each reporting period to reflect the current fair value. Under the amended guidance, we value grants to nonemployees when we grant them and we will not adjust their value for future changes. We adopted this guidance in the second quarter of 2018 on a prospective basis. The updated guidance did not have a material impact to our financial results.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 consolidated financial statements and timing of adoption.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 anticipate we will adopt this updated guidance on January 1, 2019 and we do not expect it to have a significant impact on our disclosures.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock>
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  <!--Organization, Consolidation and Presentation of Financial Statements Disclosure [Text Block]-->
  <us-gaap:OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify;"&gt;1.&amp;#160; Basis of Presentation&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended September 30, 2018 and 2017 on the same basis as the audited financial statements for the year ended December 31, 2017. 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, 2017 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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, which we formed in December 2014. &lt;/font&gt;Prior to Akcea&amp;#8217;s &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;initial public offering, or IPO,&lt;/font&gt; 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 &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;68 percent &lt;/font&gt;of Akcea. In the second and third 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. We reflected the increase in our ownership in these financial statements. In October 2018, we received an additional 1.7 million shares of Akcea&amp;#8217;s stock when TEGSEDI received marketing authorization in the U.S., increasing our ownership to approximately 76 percent. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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; color: #000000; font-style: italic;"&gt;Significant Accounting Policies,&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 Recognition, Policy [Policy Text Block]-->
  <us-gaap:RevenueRecognitionPolicyTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Revenue Recognition&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;u&gt;Adoption of New Revenue Recognition Accounting Standard (Topic 606)&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;In May 2014, the FASB issued accounting guidance on the recognition of revenue from customers. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;This guidance supersedes the revenue recognition requirements we previously followed in Accounting Standards Codification, or ASC, Topic 605, &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;"&gt;Revenue Recognition&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;, or Topic 605, and created a new Topic 606, &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;"&gt;Revenue from Contracts with Customers&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;, or Topic 606. &lt;/font&gt;Under Topic 606, an entity will recognize revenue when it transfers control of promised goods or services to customers in an amount that reflects what the entity expects to receive in exchange for the goods or services. Further, an entity will recognize revenue upon satisfying the performance obligation(s) under the related contract. We adopted Topic 606 on January 1, 2018 under the full retrospective approach, which required us to revise our prior period revenue. Under Topic 606, we were required to review all of our ongoing collaboration agreements in which we recognized revenue after January 1, 2016. We were required to assess what our revenue would have been for the period from January 1, 2016 to December 31, 2017 under Topic 606. As a result of this analysis, we determined that the cumulative revenue we would have recognized under Topic 606 decreased by $53.6 million. We recorded this amount as a cumulative adjustment to our accumulated deficit as of December 31, 2017. We have labeled our prior period financial statements &amp;#8220;as revised&amp;#8221; to indicate the change required under the accounting rules.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following tables summarize the adjustments we were required to make to amounts we originally reported in 2017 to adopt Topic 606 (in thousands, except per share amounts):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Condensed Consolidated Balance Sheet&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;At December 31, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Previously&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Reported under&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 605&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 606&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Current portion of deferred revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;106,465&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;18,871&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;125,336&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Long-term portion of deferred revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;72,708&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;35,318&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;108,026&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Accumulated deficit&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,187,398&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(53,636&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,241,034&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&amp;#160;&amp;#160;Noncontrolling interest in Akcea Therapeutics, Inc.&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;87,847&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(3,580&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;84,267&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Total stockholders&amp;#8217; equity&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;418,719&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(53,439&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;365,280&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Condensed Consolidated Statement of Operations&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Previously&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Reported under&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 605&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 606&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32,890&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32,890&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;879&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;848&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,727&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 17.75pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;33,769&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;848&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;34,617&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Research and development revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;87,142&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(3,445&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;83,697&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -9pt;"&gt;Total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;120,911&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,597&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;118,314&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr style="height: 16px;"&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;13,909&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,597&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,312&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(4,896&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,597&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(7,493&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(976&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,635&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,611&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss) per share, basic and diluted&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.00&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.02&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.02&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Previously&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Reported under&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 605&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 606&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;60,467&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;60,467&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4,983&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;656&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5,639&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 17.75pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;65,450&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;656&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;66,106&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Research and development revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;269,917&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;10,364&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;280,281&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -9pt;"&gt;Total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;335,367&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,020&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;346,387&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Income from operations&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;26,227&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,020&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;37,247&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(12,636&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,020&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,616&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(8,716&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,982&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;3,266&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss) per share, basic&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.02&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.11&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.13&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss) per share, diluted&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.02&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.11&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.13&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Condensed Consolidated Statement of Cash Flows&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Previously&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Reported under&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 605&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 606&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(12,636&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,020&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,616&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Adjustments to reconcile net income (loss) to net cash provided by operating activities:&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 36pt; text-indent: -27.15pt;"&gt;Deferred contract revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;42,091&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(11,020&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;31,071&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Cash and cash equivalents at beginning of period&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;84,685&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;84,685&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Cash and cash equivalents at end of period&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;159,184&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;159,184&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Under Topic 606, compared to Topic 605, our revenue decreased $2.6 million for the three months ended &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;September 30, 2017&lt;/font&gt;, and increased $11.0 million for the &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;nine months ended September 30, 2017&lt;/font&gt;. The change in our revenue was primarily due to:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;A change in how we recognize milestone payments:&lt;/u&gt;&lt;/font&gt; Topic 606 requires us to amortize more of the milestone payments we achieve, rather than recognizing the milestone payments in full in the period in which we achieved the milestone event as we did under Topic 605. This change resulted in an increase of $0.5 million and $27.9 million for the three and nine months ended September 30, 2017, respectively.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;A change in how we calculate revenue for payments we are recognizing into revenue over time:&lt;/u&gt;&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Under Topic 605, we amortized payments into revenue evenly over the period of our obligations. When we made a change to our estimated completion period, we recognized that change on a prospective basis. Under Topic 606, we are required to use an input method to determine the amount we amortize each reporting period. Each period, we review our &amp;#8220;inputs&amp;#8221; such as our level of effort expended, including the time we estimate it will take us to complete the activities, or costs incurred relative to the total expected inputs to satisfy the performance obligation. For certain collaborations, such as Bayer, Janssen and Novartis, the input method resulted in a change to the revenue we had previously recognized using a straight-line amortization method.&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;This change resulted in a decrease of $4.0 million and $17.5 million for the three and nine months ended September 30, 2017, respectively.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Our updated revenue recognition policy reflecting Topic 606 is as follows:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;&lt;u&gt;Our Revenue Sources&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 condensed consolidated balance sheet.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We expect to add product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 as a result of TEGSEDI&amp;#8217;s approval in the U.S., EU and Canada. We will also recognize as commercial revenue future sales milestone payments and royalties we earn under our partnerships.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Research and development revenue under collaborative agreements&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Our collaboration agreements are detailed in Note 6, &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;&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;&lt;u&gt;Steps to Recognize Revenue&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;"&gt;1.&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;"&gt;Identify the contract&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; text-indent: 36pt;"&gt;Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;We and our partner approved the contract and we are both committed to perform our obligations;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;We have identified our rights, our partner&amp;#8217;s rights and the payment terms;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;We believe collectability is probable.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;"&gt;2.&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;"&gt;Identify the performance obligations&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Often times when we enter into a collaboration agreement in which we provide our partner with an option to license a drug 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 drug 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 drug or requests additional goods or services, then we identify a new performance obligation for that item.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;"&gt;3.&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;"&gt;Determine the transaction price&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;"&gt;4.&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;"&gt;Allocate the transaction price&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Estimated future product sales;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Estimated royalties on future product sales;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Contractual milestone payments;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Expenses we expect to incur;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Income taxes; and&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;A discount rate.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We typically estimate the selling price of R&amp;amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;amp;D services include:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;The number of internal hours we estimate we will spend performing these services;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;The estimated cost of work we will perform;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;The estimated cost of work that we will contract with third parties to perform; and&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;The estimated cost of API we will use.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;For purposes of determining the stand-alone selling price of the R&amp;amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;"&gt;5.&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;"&gt;Recognize revenue&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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; color: #000000;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; text-indent: 36pt;"&gt;The following are examples of when we typically recognize revenue based on the types of payments we receive.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: left; text-indent: 36pt;"&gt;&lt;u&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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. Our accounting for SPINRAZA royalties did not change as a result of adopting Topic 606.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: left; text-indent: 36pt;"&gt;&lt;u&gt;Research and development revenue under collaboration agreements:&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: left; text-indent: 36pt;"&gt;&lt;u&gt;Upfront Payments&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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 new SMA collaboration with Biogen, we received a $25 million upfront payment in December 2017. We allocated the upfront payment to our single performance obligation, R&amp;amp;D services. We are amortizing the $25 million upfront payment using an input method over the estimated period of time we are providing R&amp;amp;D services. Refer to &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Note 6, &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements&lt;/font&gt;, for further discussion. Under Topic 605, we amortized upfront payments evenly over the period of our obligation.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;&lt;u&gt;Milestone Payments&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;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 drug is approved by the applicable regulator. 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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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. Under Topic 606, we allocated this payment to our R&amp;amp;D services performance obligation. We are recognizing revenue from this milestone payment over our estimated period of performance. Under Topic 605, this milestone payment was recognized in full in the third quarter of 2017, which was the period in which we achieved the milestone event.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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. For example, in the third quarter of 2018, we earned a $10 million milestone payment when AstraZeneca initiated a Phase 1 study of IONIS-AZ4-2.5-L&lt;sub&gt;Rx&lt;/sub&gt;. Our revenue recognition of milestone payments we earn based on our partners&amp;#8217; activities did not change as a result of adopting Topic 606.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;&lt;u&gt;License Fees&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 third quarter of 2018, we earned a $12 million license fee when our majority-owned affiliate, Akcea, &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;entered into an exclusive license agreement with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America&lt;/font&gt;. Our recognition of license fees did not change as a result of adopting Topic 606.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Amendments to Agreements&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;1)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;2)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;If the goods and/or services are at a stand-alone selling price.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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 standalone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; and to initiate development of IONIS-FXI-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; and IONIS-FXI-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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; color: #000000;"&gt;Note 6, &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; 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; color: #000000;"&gt;of our accounting treatment for our Bayer collaboration. &lt;/font&gt;Our allocation of the consideration we received for the Bayer amendment did not change as a result of adopting Topic 606. However, the method in which we are recognizing revenue related to our R&amp;amp;D services performance obligation did change. We are amortizing revenue related to our R&amp;amp;D services performance obligation using the input method under Topic 606.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Multiple Agreements&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Whether the agreements were negotiated together with a single objective;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Whether the goods and/or services promised under the agreements are a single performance obligation.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify;"&gt;Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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; color: #000000;"&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. Refer to Note 6, &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; for further discussion of the accounting treatment for the 2018 strategic neurology collaboration with Biogen.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left; margin-left: 54pt; text-indent: -18pt;"&gt;Contracts Receivable&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Our contracts receivable balance represents the amounts we have billed our partners for goods we have delivered or services we have performed that are due to us unconditionally. When we bill our partners 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&lt;/font&gt;. Our contracts receivable balance as of December 31, 2017 did not change when we adopted Topic 606.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; margin-left: 54pt; text-indent: -18pt;"&gt;Unbilled SPINRAZA Royalties&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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;Our unbilled SPINRAZA royalties as of December 31, 2017 did not change when we adopted Topic 606.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left; margin-left: 54pt; text-indent: -18pt;"&gt;Deferred Revenue&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 and nine months ended September 30, 2018, we recognized $37.2 million and $80.4 million of revenue from amounts that were in our beginning deferred revenue balances for those periods, respectively. During the three and nine months ended September 30, 2017, we recognized $31.6 million and $84.4 million of revenue from amounts that were in our beginning deferred revenue balances for those periods, respectively. Refer to our revenue recognition policy above detailing how we recognize revenue for further discussion.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following table summarizes the adjustments we were required to make to our deferred revenue amounts to adopt Topic 606 (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="11" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;At December 31, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Previously&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Reported under&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 605&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 606&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Current portion of deferred revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;106,465&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;18,871&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;125,336&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Long-term portion of deferred revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;72,708&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;35,318&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;108,026&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt;"&gt;Total deferred revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;179,173&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;54,189&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;233,362&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Our deferred revenue balance increased $54.2 million at December 31, 2017 under Topic 606, compared to Topic 605. The increase was primarily related to the change in the accounting for certain milestone payments and the way in which we amortize payments. Under Topic 605, we previously recognized the majority of the milestone payments we earned in the period we achieved the milestone event, which did not impact our deferred revenue balance. Under Topic 606 we are now amortizing more milestone payments over the period of our performance obligation, which adds to our deferred revenue balance. Additionally, under Topic 605 we amortized payments evenly over the period of our obligation. Under Topic 606, we are required to use an input method to determine the amount we amortize each reporting period. The increase in deferred revenue relates to agreements with the following partners:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$24.2 million from Biogen;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$15.9 million from AstraZeneca;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$11.8 from Novartis; and&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$2.3 million from other partners.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&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:SaleOfStockPercentageOfOwnershipBeforeTransaction contextRef="c20170101to20170731_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="INF">1</us-gaap:SaleOfStockPercentageOfOwnershipBeforeTransaction>
  <!--Schedule of Revenue by Major Customers by Reporting Segments [Table Text Block]-->
  <us-gaap:ScheduleOfRevenueByMajorCustomersByReportingSegmentsTableTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We have historically funded our operations from collaborations with corporate partners and a relatively small number of partners have accounted for a significant percentage of our revenue. Revenue from significant partners, which is defined as ten percent or more of our total revenue, was as follows:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%; border-collapse: collapse;"&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="5" style="width: 30%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="5" style="width: 27.68%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="2" style="width: 16.01%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.68%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="2" style="width: 12.31%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="2" style="width: 11.61%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="2" style="width: 14.24%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.92%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 14.09%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.67%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.64%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: right;"&gt;(as revised)&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.88%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 9.73%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 12.42%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: right;"&gt;(as revised)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Partner A&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.92%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 14.09%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;72%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.67%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 10.64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;74%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.88%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 9.73%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;58%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 12.42%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;57%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Partner B&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.92%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 14.09%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;10%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.67%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 10.64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;4%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.88%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 9.73%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;21%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 12.42%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;4%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Partner C&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.92%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 14.09%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;5%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.67%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 10.64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;8%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.88%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 9.73%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;10%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 12.42%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;6%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Partner D&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.92%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 14.09%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;8%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.67%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.88%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 9.73%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;&amp;#160;3%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 12.42%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;&amp;#160;0%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Partner E&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.92%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 14.09%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;1%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.67%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.88%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 9.73%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;1%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 12.42%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;19%&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:ScheduleOfRevenueByMajorCustomersByReportingSegmentsTableTextBlock>
  <!--Schedule of Share-based Payment Award, Employee Stock Purchase Plan, Valuation Assumptions [Table Text Block]-->
  <us-gaap:ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;ESPP:&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 60%; border-collapse: collapse;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;1.8%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.8%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;47.3%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;59.9%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;6 months&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;6 months&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="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 nine months ended September 30, 2018 and 2017, 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; text-indent: 36pt;"&gt;Employee Stock Options:&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 60%; border-collapse: collapse;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;2.3%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;1.8%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;63.1%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;66.1%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;4.6 years&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;4.5 years&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&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; text-indent: 36pt;"&gt;Board of Director Stock Options:&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 60%; border-collapse: collapse;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;2.8 %&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;2.2 %&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0 %&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0 %&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;61.5 %&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;61.2 %&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;6.6 years&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;6.6 years&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="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;For the nine months ended September 30, 2017, 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 those periods. Diluted common equivalent shares for the nine months ended September 30, 2017 consisted of the following (in thousands except per share amounts):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Nine months ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Income&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Shares&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Per-Share&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Amount&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16,321&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;123,746&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.13&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -8.9pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,658&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: 0.1pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;430&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; text-indent: 9.1pt;"&gt;Shares issuable related to our ESPP&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;24&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Income available to Ionis common stockholders, plus assumed conversions&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16,321&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;125,858&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.13&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;For the nine months ended September 30, 2017, the calculation excluded the 1 percent and 2&amp;#190; 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;</us-gaap:ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock>
  <!--Schedule of Temporary Impairment Losses, Investments [Table Text Block]-->
  <us-gaap:ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following is a summary of our investments we consider to be temporarily impaired at September 30, 2018. 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-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 30%; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7px; vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="2" valign="bottom" style="vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Less than 12 Months of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Temporary Impairment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;More than 12 Months of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Temporary Impairment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Total Temporary&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Impairment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 30%; vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;(In thousands)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7px; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Number of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Investments&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Estimated&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Unrealized&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Losses&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Estimated&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Unrealized&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Losses&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Estimated&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Unrealized&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Losses&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 30%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7px; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;495&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;889,172&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,687&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;83,706&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(997&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;972,878&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,684&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 30%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7px; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;51&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;132,231&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(139&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;26,862&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(139&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;159,093&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(278&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 30%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7px; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;164,053&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(99&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;164,053&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(99&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 30%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7px; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;48&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;25,687&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(191&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;51,747&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(690&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;77,434&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(881&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 30%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Total temporarily impaired securities&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7px; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;626&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,211,143&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,116&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;162,315&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,826&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,373,458&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(3,942&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 Accumulated Other Comprehensive Income (Loss) [Table Text Block]-->
  <us-gaap:ScheduleOfAccumulatedOtherComprehensiveIncomeLossTableTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We include unrealized gains and losses on investments, net of taxes, in accumulated other comprehensive income (loss) along with&amp;#160;adjustments we make to reclassify realized gains and losses on investments from other accumulated comprehensive income (loss) to our condensed consolidated statement of operations. The following table summarizes changes in accumulated other comprehensive income (loss) for the three and nine months ended September 30, 2018 and 2017 (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 90%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Beginning balance accumulated other comprehensive loss&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(32,637&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(30,372&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(31,759&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(30,358&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Unrealized gains (losses) on securities (1)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;133&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;215&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(834&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;610&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Amounts reclassified from accumulated other comprehensive loss&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(374&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Currency translation adjustment&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(28&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(42&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;61&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(77&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net current period other comprehensive income (loss)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;105&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;173&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(773&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;159&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Ending balance accumulated other comprehensive loss&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(32,532&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(30,199&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(32,532&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(30,199&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;(1)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;There was no income tax expense or benefit related to elements of other comprehensive income (loss) for the three and nine months ended September 30, 2018 and 2017.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ScheduleOfAccumulatedOtherComprehensiveIncomeLossTableTextBlock>
  <!--Schedule of Earnings Per Share, Basic, by Common Class, Including Two Class Method [Table Text Block]-->
  <us-gaap:ScheduleOfEarningsPerShareBasicByCommonClassTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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; color: #000000;"&gt;September 30, 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 align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Three months ended September 30, 2018&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Weighted&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Average Shares&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Net Income (Loss)&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis&amp;#8217; Portion of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s Net Loss&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;65,538&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.73&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(47,843&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Akcea&amp;#8217;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(47,843&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Ionis&amp;#8217; stand-alone net income&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;43,226&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(4,616&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;143,314&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.03&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following table summarizes stock-based compensation expense for the three and nine months ended September 30, 2018 and 2017 (in thousands). Our consolidated non-cash stock-based compensation expense includes $12.7 million and $4.7 million of stock-based compensation expense for Akcea for the three months ended September 30, 2018 and 2017, respectively, and $31.2 million and $11.8 million for the nine months ended September 30, 2018 and 2017, respectively.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Research, development and patent&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;18,780&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16,181&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;57,698&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;48,443&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Selling, general and administrative&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16,103&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5,291&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;39,512&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;15,199&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Total non-cash stock-based compensation expense&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;34,883&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;21,472&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;97,210&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;63,642&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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:ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock>
  <!--Schedule of New Accounting Pronouncements and Changes in Accounting Principles [Table Text Block]-->
  <us-gaap:ScheduleOfNewAccountingPronouncementsAndChangesInAccountingPrinciplesTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following tables summarize the adjustments we were required to make to amounts we originally reported in 2017 to adopt Topic 606 (in thousands, except per share amounts):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Condensed Consolidated Balance Sheet&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;At December 31, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Previously&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Reported under&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 605&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 606&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Current portion of deferred revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;106,465&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;18,871&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;125,336&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Long-term portion of deferred revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;72,708&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;35,318&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;108,026&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Accumulated deficit&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,187,398&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(53,636&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,241,034&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&amp;#160;&amp;#160;Noncontrolling interest in Akcea Therapeutics, Inc.&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;87,847&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(3,580&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;84,267&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Total stockholders&amp;#8217; equity&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;418,719&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(53,439&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;365,280&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Condensed Consolidated Statement of Operations&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Previously&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Reported under&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 605&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 606&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32,890&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32,890&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;879&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;848&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,727&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 17.75pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;33,769&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;848&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;34,617&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Research and development revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;87,142&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(3,445&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;83,697&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -9pt;"&gt;Total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;120,911&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,597&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;118,314&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr style="height: 16px;"&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;13,909&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,597&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,312&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(4,896&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,597&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(7,493&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(976&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,635&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,611&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss) per share, basic and diluted&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.00&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.02&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.02&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Previously&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Reported under&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 605&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 606&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;60,467&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;60,467&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4,983&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;656&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5,639&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 17.75pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;65,450&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;656&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;66,106&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Research and development revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;269,917&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;10,364&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;280,281&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -9pt;"&gt;Total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;335,367&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,020&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;346,387&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Income from operations&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;26,227&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,020&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;37,247&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(12,636&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,020&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,616&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(8,716&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,982&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;3,266&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss) per share, basic&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.02&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.11&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.13&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss) per share, diluted&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.02&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.11&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.13&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Condensed Consolidated Statement of Cash Flows&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Previously&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Reported under&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 605&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 606&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(12,636&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,020&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,616&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Adjustments to reconcile net income (loss) to net cash provided by operating activities:&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 36pt; text-indent: -27.15pt;"&gt;Deferred contract revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;42,091&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(11,020&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;31,071&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Cash and cash equivalents at beginning of period&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;84,685&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;84,685&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Cash and cash equivalents at end of period&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;159,184&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;159,184&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following table summarizes the adjustments we were required to make to our deferred revenue amounts to adopt Topic 606 (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="11" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;At December 31, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Previously&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Reported under&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 605&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 606&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Current portion of deferred revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;106,465&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;18,871&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;125,336&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Long-term portion of deferred revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;72,708&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;35,318&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;108,026&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt;"&gt;Total deferred revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;179,173&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;54,189&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;233,362&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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:ScheduleOfNewAccountingPronouncementsAndChangesInAccountingPrinciplesTextBlock>
  <!--Segment Information-->
  <us-gaap:ScheduleOfSegmentReportingInformationBySegmentTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following tables show our segment revenue and income (loss) from operations for the three and nine months ended September 30, 2018 and 2017 (in thousands), respectively.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Three Months Ended September 30, 2018&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Elimination of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;70,010&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;70,010&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;7,946&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12,000&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12,746&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 43.2pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;77,956&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12,000&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;82,756&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;100,105&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;7,241&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(44,707&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;62,639&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;178,061&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;19,241&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(51,907&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;145,395&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;87,664&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;84,249&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(7,946&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;163,967&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;90,397&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(65,008&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(43,961&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(18,572&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Three Months Ended September 30, 2017 (as revised)&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Elimination of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32,890&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32,890&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,727&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,727&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 43.2pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;34,617&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;34,617&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;73,791&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;9,906&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;83,697&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;108,408&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;9,906&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;118,314&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;81,019&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;26,013&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(30&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;107,002&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;27,389&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(16,107&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;30&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,312&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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;table cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Nine Months Ended September 30, 2018&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Elimination of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;167,743&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;167,743&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;9,432&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12,000&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;14,232&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 43.2pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;177,175&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12,000&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;181,975&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;232,850&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;42,670&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(49,936&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;225,584&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;410,025&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;54,670&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(57,136&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;407,559&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;279,084&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;213,428&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(12,796&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;479,716&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;130,941&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(158,758&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(44,340&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(72,157&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Nine Months Ended September 30, 2017 (as revised)&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Elimination of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;60,467&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;60,467&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5,639&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5,639&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 43.2pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;66,106&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;66,106&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;312,976&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;21,712&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(54,407&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;280,281&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;379,082&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;21,712&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(54,407&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;346,387&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;242,753&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;120,884&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(54,497&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;309,140&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;136,329&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(99,172&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;90&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;37,247&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following table shows our total assets by segment at September 30, 2018 and December 31, 2017 (in thousands), respectively.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 42%; vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Total Assets&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Elimination of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 42%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;September 30, 2018&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;2,446,425&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;379,128&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(577,641&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;2,247,913&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 42%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;December 31, 2017 (as revised)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,342,578&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;268,804&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(288,608&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,322,774&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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, AstraZeneca [Member]-->
  <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock contextRef="c20180101to20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsAstraZenecaMember">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with AstraZeneca (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;14.2&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4.8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;86.5&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;14.8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;10&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;21&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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, Bayer [Member]-->
  <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock contextRef="c20180101to20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBayerMember">&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Bayer (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1.9&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;3.3&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;66.0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;19&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 December 2014 with Janssen Biotech, Inc. [Member]-->
  <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock contextRef="c20180101to20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Janssen (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.9&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;3.4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;6.6&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;18.1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;3&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;2&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="c20180101to20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;7.2&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;9.9&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;42.7&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;21.7&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;10&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;6&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="c20180101to20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;SPINRAZA royalties (commercial revenue)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;70.0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32.9&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;167.7&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;60.5&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;34.8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;54.9&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;66.9&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;137.1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -9pt;"&gt;Total revenue from our relationship with Biogen&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;104.8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;87.8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;234.6&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;197.6&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;72&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;74&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;58&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;57&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 March 2010 with GSK [Member]-->
  <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock contextRef="c20180101to20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with GSK (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4.6&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1.5&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;14.4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 August 2018 with PTC Therapeutics [Member]-->
  <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock contextRef="c20180101to20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with PTC (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12.0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12.0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.0&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;3&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; 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:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock>
  <!--Schedules of Concentration of Risk, by Risk Factor [Table Text Block]-Collaborative Arrangements and Licensing Agreements, Roche [Member]-->
  <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock contextRef="c20180101to20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;During the three and nine months ended September 30, 2018 and 2017, 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1.8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4.5&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5.4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5.9&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;%&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;2&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Segment information&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 drugs to treat patients with rare and serious diseases&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:SegmentReportingPolicyPolicyTextBlock>
  <!--Segment Information and Concentration of Business Risk-->
  <us-gaap:SegmentReportingDisclosureTextBlock contextRef="c20180101to20180930">&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;7.&amp;#160; Segment Information and Concentration of Business Risk&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;We have two reportable segments Ionis Core and Akcea Therapeutics. &lt;/font&gt;At September 30, 2018 we owned approximately 75 percent of Akcea.&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#160;&lt;/font&gt;In October 2018, we received an additional 1.7 million shares of Akcea&amp;#8217;s stock when TEGSEDI was approved by the FDA, increasing our ownership percentage to 76 percent. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Segment income (loss) from operations includes revenue less operating expenses attributable to each segment.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 drugs for us and our partners. Our Ionis Core segment generates revenue from a multifaceted partnering strategy.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Akcea is &lt;/font&gt;a biopharmaceutical company focused on developing and commercializing drugs to treat patients with rare and serious diseases&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following tables show our segment revenue and income (loss) from operations for the three and nine months ended September 30, 2018 and 2017 (in thousands), respectively.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Three Months Ended September 30, 2018&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Elimination of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;70,010&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;70,010&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;7,946&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12,000&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12,746&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 43.2pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;77,956&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12,000&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;82,756&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;100,105&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;7,241&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(44,707&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;62,639&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;178,061&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;19,241&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(51,907&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;145,395&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;87,664&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;84,249&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(7,946&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;163,967&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;90,397&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(65,008&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(43,961&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(18,572&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Three Months Ended September 30, 2017 (as revised)&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Elimination of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32,890&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32,890&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,727&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,727&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 43.2pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;34,617&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;34,617&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;73,791&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;9,906&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;83,697&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;108,408&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;9,906&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;118,314&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;81,019&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;26,013&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(30&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;107,002&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;27,389&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(16,107&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;30&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,312&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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;table cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Nine Months Ended September 30, 2018&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Elimination of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;167,743&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;167,743&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;9,432&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12,000&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;14,232&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 43.2pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;177,175&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12,000&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;181,975&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;232,850&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;42,670&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(49,936&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;225,584&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;410,025&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;54,670&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(57,136&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;407,559&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;279,084&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;213,428&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(12,796&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;479,716&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;130,941&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(158,758&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(44,340&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(72,157&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Nine Months Ended September 30, 2017 (as revised)&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Elimination of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: top;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;60,467&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;60,467&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5,639&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5,639&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 43.2pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;66,106&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;66,106&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;312,976&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;21,712&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(54,407&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;280,281&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;379,082&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;21,712&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(54,407&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;346,387&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;242,753&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;120,884&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(54,497&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;309,140&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;136,329&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(99,172&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;90&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;37,247&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following table shows our total assets by segment at September 30, 2018 and December 31, 2017 (in thousands), respectively.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 42%; vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Total Assets&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Elimination of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Total&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 42%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;September 30, 2018&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;2,446,425&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;379,128&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(577,641&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;2,247,913&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 42%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;"&gt;December 31, 2017 (as revised)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,342,578&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;268,804&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(288,608&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,322,774&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We have historically funded our operations from collaborations with corporate partners and a relatively small number of partners have accounted for a significant percentage of our revenue. Revenue from significant partners, which is defined as ten percent or more of our total revenue, was as follows:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%; border-collapse: collapse;"&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="5" style="width: 30%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="5" style="width: 27.68%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="2" style="width: 16.01%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.68%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="2" style="width: 12.31%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="2" style="width: 11.61%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td colspan="2" style="width: 14.24%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.92%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 14.09%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.68%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.67%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.64%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: right;"&gt;(as revised)&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.88%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 9.73%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 12.42%; vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: right;"&gt;(as revised)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Partner A&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.92%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 14.09%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;72%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.67%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 10.64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;74%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.88%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 9.73%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;58%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 12.42%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;57%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Partner B&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.92%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 14.09%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;10%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.67%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 10.64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;4%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.88%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 9.73%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;21%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 12.42%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;4%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Partner C&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.92%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 14.09%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;5%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.67%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 10.64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;8%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.88%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 9.73%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;10%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 12.42%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;6%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Partner D&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.92%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 14.09%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;8%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.67%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.88%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 9.73%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;&amp;#160;3%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 12.42%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;&amp;#160;0%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 40.55%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Partner E&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.92%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 14.09%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;1%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.67%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.77%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.88%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 9.73%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;1%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 1.83%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 12.42%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;19%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Contracts receivables from two significant partners comprised approximately 84 percent of our contracts receivables at September 30, 2018 and December 31, 2017.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:SegmentReportingDisclosureTextBlock>
  <!--Selling, General and Administrative Expense-->
  <us-gaap:SellingGeneralAndAdministrativeExpense contextRef="c20180101to20180930" unitRef="U002" decimals="-3">178563000</us-gaap:SellingGeneralAndAdministrativeExpense>
  <!--Selling, General and Administrative Expense-->
  <us-gaap:SellingGeneralAndAdministrativeExpense contextRef="c20180701to20180930" unitRef="U002" decimals="-3">68712000</us-gaap:SellingGeneralAndAdministrativeExpense>
  <!--Selling, General and Administrative Expense-->
  <us-gaap:SellingGeneralAndAdministrativeExpense contextRef="c20170101to20170930" unitRef="U002" decimals="-3">62782000</us-gaap:SellingGeneralAndAdministrativeExpense>
  <!--Selling, General and Administrative Expense-->
  <us-gaap:SellingGeneralAndAdministrativeExpense contextRef="c20170701to20170930" unitRef="U002" decimals="-3">26788000</us-gaap:SellingGeneralAndAdministrativeExpense>
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  <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1 contextRef="c20180101to20180930_AwardTypeAxis_RestrictedStockUnitsRSUMember">P4Y</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1>
  <!--Share-based Compensation-->
  <us-gaap:ShareBasedCompensation contextRef="c20170101to20170930" unitRef="U002" decimals="-3">63642000</us-gaap:ShareBasedCompensation>
  <!--Share-based Compensation-->
  <us-gaap:ShareBasedCompensation contextRef="c20180101to20180930" unitRef="U002" decimals="-3">97210000</us-gaap:ShareBasedCompensation>
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  <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate contextRef="c20170101to20170930_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U003" decimals="3">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
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  <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate contextRef="c20170101to20170930_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
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  <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U003" decimals="3">0.631</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
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  <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate contextRef="c20170101to20170930_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U003" decimals="3">0.018</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
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  <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3">0.018</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
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  <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U003" decimals="3">0.023</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
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  <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate contextRef="c20170101to20170930_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3">0.008</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Risk Free Interest Rate-Board of Director Stock Option [Member]-->
  <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember" unitRef="U003" decimals="3">0.028</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
  <!--Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Risk Free Interest Rate-Board of Director Stock Option [Member]-->
  <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate contextRef="c20170101to20170930_AwardTypeAxis_BoardOfDirectorStockOptionMember" unitRef="U003" decimals="3">0.022</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
  <!--Weighted-average grant date fair value (in dollars per share)-Employee [Member]-Restricted Stock Units (RSUs) [Member]-->
  <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue contextRef="c20180101to20180930_AwardTypeAxis_RestrictedStockUnitsRSUMember_RelatedPartyTransactionsByRelatedPartyAxis_EmployeeMember" unitRef="U004" decimals="2">51.83</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue>
  <!--Weighted-average grant date fair value (in dollars per share)-Board of Directors [Member]-Restricted Stock Units (RSUs) [Member]-->
  <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue contextRef="c20180101to20180930_AwardTypeAxis_RestrictedStockUnitsRSUMember_RelatedPartyTransactionsByRelatedPartyAxis_BoardOfDirectorsMember" unitRef="U004" decimals="2">42.88</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue>
  <!--Share-based Compensation, Option and Incentive Plans Policy [Policy Text Block]-->
  <us-gaap:ShareBasedCompensationOptionAndIncentivePlansPolicy contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Stock-based compensation expense&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 nine months ended September 30, 2018 and 2017, 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; text-indent: 36pt;"&gt;Employee Stock Options:&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 60%; border-collapse: collapse;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;2.3%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;1.8%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;63.1%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;66.1%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;4.6 years&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;4.5 years&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&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; text-indent: 36pt;"&gt;Board of Director Stock Options:&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 60%; border-collapse: collapse;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;2.8 %&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;2.2 %&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0 %&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0 %&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;61.5 %&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;61.2 %&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;6.6 years&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;6.6 years&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;ESPP:&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 60%; border-collapse: collapse;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;1.8%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.8%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;47.3%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;59.9%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;6 months&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;6 months&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 and members of our board of directors for the nine months ended September 30, 2018 was $51.83 and $42.88 per share, respectively.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following table summarizes stock-based compensation expense for the three and nine months ended September 30, 2018 and 2017 (in thousands). Our consolidated non-cash stock-based compensation expense includes $12.7 million and $4.7 million of stock-based compensation expense for Akcea for the three months ended September 30, 2018 and 2017, respectively, and $31.2 million and $11.8 million for the nine months ended September 30, 2018 and 2017, respectively.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Research, development and patent&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;18,780&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16,181&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;57,698&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;48,443&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Selling, general and administrative&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16,103&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5,291&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;39,512&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;15,199&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Total non-cash stock-based compensation expense&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;34,883&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;21,472&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;97,210&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;63,642&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;As of September 30, 2018, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options and RSUs was $139.5 million and $32.6 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 1.3 years and 1.6 years, respectively.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:ShareBasedCompensationOptionAndIncentivePlansPolicy>
  <!--Significant Accounting Policies [Text Block]-->
  <us-gaap:SignificantAccountingPoliciesTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;2.&amp;#160; Significant Accounting Policies&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Revenue Recognition&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;u&gt;Adoption of New Revenue Recognition Accounting Standard (Topic 606)&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;In May 2014, the FASB issued accounting guidance on the recognition of revenue from customers. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;This guidance supersedes the revenue recognition requirements we previously followed in Accounting Standards Codification, or ASC, Topic 605, &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;"&gt;Revenue Recognition&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;, or Topic 605, and created a new Topic 606, &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;"&gt;Revenue from Contracts with Customers&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;, or Topic 606. &lt;/font&gt;Under Topic 606, an entity will recognize revenue when it transfers control of promised goods or services to customers in an amount that reflects what the entity expects to receive in exchange for the goods or services. Further, an entity will recognize revenue upon satisfying the performance obligation(s) under the related contract. We adopted Topic 606 on January 1, 2018 under the full retrospective approach, which required us to revise our prior period revenue. Under Topic 606, we were required to review all of our ongoing collaboration agreements in which we recognized revenue after January 1, 2016. We were required to assess what our revenue would have been for the period from January 1, 2016 to December 31, 2017 under Topic 606. As a result of this analysis, we determined that the cumulative revenue we would have recognized under Topic 606 decreased by $53.6 million. We recorded this amount as a cumulative adjustment to our accumulated deficit as of December 31, 2017. We have labeled our prior period financial statements &amp;#8220;as revised&amp;#8221; to indicate the change required under the accounting rules.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following tables summarize the adjustments we were required to make to amounts we originally reported in 2017 to adopt Topic 606 (in thousands, except per share amounts):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Condensed Consolidated Balance Sheet&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;At December 31, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Previously&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Reported under&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 605&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 606&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Current portion of deferred revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;106,465&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;18,871&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;125,336&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Long-term portion of deferred revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;72,708&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;35,318&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;108,026&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Accumulated deficit&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,187,398&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(53,636&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,241,034&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&amp;#160;&amp;#160;Noncontrolling interest in Akcea Therapeutics, Inc.&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;87,847&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(3,580&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;84,267&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Total stockholders&amp;#8217; equity&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;418,719&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(53,439&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;365,280&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Condensed Consolidated Statement of Operations&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Previously&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Reported under&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 605&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 606&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32,890&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32,890&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;879&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;848&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,727&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 17.75pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;33,769&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;848&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;34,617&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Research and development revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;87,142&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(3,445&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;83,697&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -9pt;"&gt;Total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;120,911&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,597&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;118,314&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr style="height: 16px;"&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;13,909&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,597&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,312&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(4,896&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,597&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(7,493&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(976&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,635&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,611&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss) per share, basic and diluted&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.00&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.02&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.02&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Previously&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Reported under&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 605&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 606&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;60,467&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;60,467&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4,983&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;656&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5,639&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 17.75pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;65,450&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;656&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;66,106&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Research and development revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;269,917&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;10,364&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;280,281&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -9pt;"&gt;Total revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;335,367&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,020&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;346,387&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Income from operations&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;26,227&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,020&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;37,247&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(12,636&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,020&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,616&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(8,716&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,982&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;3,266&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss) per share, basic&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.02&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.11&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.13&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss) per share, diluted&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.02&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.11&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.13&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Condensed Consolidated Statement of Cash Flows&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Previously&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Reported under&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 605&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 606&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income (loss)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(12,636&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;11,020&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,616&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Adjustments to reconcile net income (loss) to net cash provided by operating activities:&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 36pt; text-indent: -27.15pt;"&gt;Deferred contract revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;42,091&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(11,020&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;31,071&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Cash and cash equivalents at beginning of period&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;84,685&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;84,685&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Cash and cash equivalents at end of period&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;159,184&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;159,184&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Under Topic 606, compared to Topic 605, our revenue decreased $2.6 million for the three months ended &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;September 30, 2017&lt;/font&gt;, and increased $11.0 million for the &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;nine months ended September 30, 2017&lt;/font&gt;. The change in our revenue was primarily due to:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;A change in how we recognize milestone payments:&lt;/u&gt;&lt;/font&gt; Topic 606 requires us to amortize more of the milestone payments we achieve, rather than recognizing the milestone payments in full in the period in which we achieved the milestone event as we did under Topic 605. This change resulted in an increase of $0.5 million and $27.9 million for the three and nine months ended September 30, 2017, respectively.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;u&gt;A change in how we calculate revenue for payments we are recognizing into revenue over time:&lt;/u&gt;&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Under Topic 605, we amortized payments into revenue evenly over the period of our obligations. When we made a change to our estimated completion period, we recognized that change on a prospective basis. Under Topic 606, we are required to use an input method to determine the amount we amortize each reporting period. Each period, we review our &amp;#8220;inputs&amp;#8221; such as our level of effort expended, including the time we estimate it will take us to complete the activities, or costs incurred relative to the total expected inputs to satisfy the performance obligation. For certain collaborations, such as Bayer, Janssen and Novartis, the input method resulted in a change to the revenue we had previously recognized using a straight-line amortization method.&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&amp;#160;&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;This change resulted in a decrease of $4.0 million and $17.5 million for the three and nine months ended September 30, 2017, respectively.&lt;/font&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Our updated revenue recognition policy reflecting Topic 606 is as follows:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;&lt;u&gt;Our Revenue Sources&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 condensed consolidated balance sheet.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We expect to add product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 as a result of TEGSEDI&amp;#8217;s approval in the U.S., EU and Canada. We will also recognize as commercial revenue future sales milestone payments and royalties we earn under our partnerships.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Research and development revenue under collaborative agreements&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Our collaboration agreements are detailed in Note 6, &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;&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;&lt;u&gt;Steps to Recognize Revenue&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;"&gt;1.&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;"&gt;Identify the contract&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; text-indent: 36pt;"&gt;Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;We and our partner approved the contract and we are both committed to perform our obligations;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;We have identified our rights, our partner&amp;#8217;s rights and the payment terms;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;We believe collectability is probable.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;"&gt;2.&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;"&gt;Identify the performance obligations&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Often times when we enter into a collaboration agreement in which we provide our partner with an option to license a drug 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 drug 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 drug or requests additional goods or services, then we identify a new performance obligation for that item.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;"&gt;3.&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;"&gt;Determine the transaction price&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;"&gt;4.&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;"&gt;Allocate the transaction price&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Estimated future product sales;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Estimated royalties on future product sales;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Contractual milestone payments;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Expenses we expect to incur;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Income taxes; and&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;A discount rate.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We typically estimate the selling price of R&amp;amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;amp;D services include:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;The number of internal hours we estimate we will spend performing these services;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;The estimated cost of work we will perform;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;The estimated cost of work that we will contract with third parties to perform; and&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;The estimated cost of API we will use.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;For purposes of determining the stand-alone selling price of the R&amp;amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;"&gt;5.&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;"&gt;Recognize revenue&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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; color: #000000;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; text-indent: 36pt;"&gt;The following are examples of when we typically recognize revenue based on the types of payments we receive.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: left; text-indent: 36pt;"&gt;&lt;u&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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. Our accounting for SPINRAZA royalties did not change as a result of adopting Topic 606.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: left; text-indent: 36pt;"&gt;&lt;u&gt;Research and development revenue under collaboration agreements:&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: left; text-indent: 36pt;"&gt;&lt;u&gt;Upfront Payments&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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 new SMA collaboration with Biogen, we received a $25 million upfront payment in December 2017. We allocated the upfront payment to our single performance obligation, R&amp;amp;D services. We are amortizing the $25 million upfront payment using an input method over the estimated period of time we are providing R&amp;amp;D services. Refer to &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Note 6, &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements&lt;/font&gt;, for further discussion. Under Topic 605, we amortized upfront payments evenly over the period of our obligation.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;&lt;u&gt;Milestone Payments&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;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 drug is approved by the applicable regulator. 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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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. Under Topic 606, we allocated this payment to our R&amp;amp;D services performance obligation. We are recognizing revenue from this milestone payment over our estimated period of performance. Under Topic 605, this milestone payment was recognized in full in the third quarter of 2017, which was the period in which we achieved the milestone event.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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. For example, in the third quarter of 2018, we earned a $10 million milestone payment when AstraZeneca initiated a Phase 1 study of IONIS-AZ4-2.5-L&lt;sub&gt;Rx&lt;/sub&gt;. Our revenue recognition of milestone payments we earn based on our partners&amp;#8217; activities did not change as a result of adopting Topic 606.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;&lt;u&gt;License Fees&lt;/u&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 third quarter of 2018, we earned a $12 million license fee when our majority-owned affiliate, Akcea, &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;entered into an exclusive license agreement with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America&lt;/font&gt;. Our recognition of license fees did not change as a result of adopting Topic 606.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Amendments to Agreements&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;1)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;2)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;If the goods and/or services are at a stand-alone selling price.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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 standalone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; and to initiate development of IONIS-FXI-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; and IONIS-FXI-L&lt;/font&gt;&lt;sub style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 style="color: #000000;"&gt;Rx&lt;/sub&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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; color: #000000;"&gt;Note 6, &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; 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; color: #000000;"&gt;of our accounting treatment for our Bayer collaboration. &lt;/font&gt;Our allocation of the consideration we received for the Bayer amendment did not change as a result of adopting Topic 606. However, the method in which we are recognizing revenue related to our R&amp;amp;D services performance obligation did change. We are amortizing revenue related to our R&amp;amp;D services performance obligation using the input method under Topic 606.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Multiple Agreements&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Whether the agreements were negotiated together with a single objective;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Whether the goods and/or services promised under the agreements are a single performance obligation.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify;"&gt;Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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; color: #000000;"&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. Refer to Note 6, &lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements&lt;/font&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt; for further discussion of the accounting treatment for the 2018 strategic neurology collaboration with Biogen.&lt;/font&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left; margin-left: 54pt; text-indent: -18pt;"&gt;Contracts Receivable&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Our contracts receivable balance represents the amounts we have billed our partners for goods we have delivered or services we have performed that are due to us unconditionally. When we bill our partners 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&lt;/font&gt;. Our contracts receivable balance as of December 31, 2017 did not change when we adopted Topic 606.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; margin-left: 54pt; text-indent: -18pt;"&gt;Unbilled SPINRAZA Royalties&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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;Our unbilled SPINRAZA royalties as of December 31, 2017 did not change when we adopted Topic 606.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left; margin-left: 54pt; text-indent: -18pt;"&gt;Deferred Revenue&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 and nine months ended September 30, 2018, we recognized $37.2 million and $80.4 million of revenue from amounts that were in our beginning deferred revenue balances for those periods, respectively. During the three and nine months ended September 30, 2017, we recognized $31.6 million and $84.4 million of revenue from amounts that were in our beginning deferred revenue balances for those periods, respectively. Refer to our revenue recognition policy above detailing how we recognize revenue for further discussion.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following table summarizes the adjustments we were required to make to our deferred revenue amounts to adopt Topic 606 (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="11" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;At December 31, 2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Previously&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Reported under&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 605&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Topic 606&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Current portion of deferred revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;106,465&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;18,871&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;125,336&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;Long-term portion of deferred revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;72,708&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;35,318&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;108,026&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt;"&gt;Total deferred revenue&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;179,173&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;54,189&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;233,362&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Our deferred revenue balance increased $54.2 million at December 31, 2017 under Topic 606, compared to Topic 605. The increase was primarily related to the change in the accounting for certain milestone payments and the way in which we amortize payments. Under Topic 605, we previously recognized the majority of the milestone payments we earned in the period we achieved the milestone event, which did not impact our deferred revenue balance. Under Topic 606 we are now amortizing more milestone payments over the period of our performance obligation, which adds to our deferred revenue balance. Additionally, under Topic 605 we amortized payments evenly over the period of our obligation. Under Topic 606, we are required to use an input method to determine the amount we amortize each reporting period. The increase in deferred revenue relates to agreements with the following partners:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$24.2 million from Biogen;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$15.9 million from AstraZeneca;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$11.8 from Novartis; and&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$2.3 million from other partners.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Noncontrolling Interest in Akcea Therapeutics, Inc.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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; color: #000000;"&gt;&amp;#160;&lt;/font&gt;of Akcea. In the second and third 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. We reflected this increase in our ownership percentage in these financial statements as an adjustment to noncontrolling interest. In October 2018, we received an additional 1.7 million shares of Akcea&amp;#8217;s stock when TEGSEDI received marketing authorization in the U.S., increasing our ownership to approximately 76 percent. &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Cash, cash equivalents and investments&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At September 30, 2018, we held an equity investment in one publicly held company, 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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In January 2018, we adopted the amended accounting guidance related to the recognition, measurement, presentation, and disclosure of certain financial instruments. The amended guidance requires us to measure and record our equity investments at fair value. Additionally, the amended accounting guidance requires us to recognize the changes in fair value in our consolidated statement of operations, instead of through accumulated other comprehensive income. Prior to 2018, we accounted for our equity investments in privately held companies under the cost method of accounting. Under the amended guidance we account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. Our adoption of this guidance did not have an impact on our results.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Inventory valuation&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;We reflect our inventory on our 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 drugs because until we use these raw materials they have alternative future uses. We include in inventory raw material costs for drugs 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 drug. For example, if one of our drugs failed, we could use the raw materials for that drug to manufacture our other drugs. We expense these costs as R&amp;amp;D expenses when we begin to manufacture API for a particular drug if the drug has not been approved for marketing by a regulatory agency.&lt;/div&gt;&lt;div style="text-align: justify;"&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;We obtained the first regulatory approval for TEGSEDI in July 2018. At September 30, 2018 and December 31, 2017, 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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 drugs and historical write-offs. We did not record any inventory write-offs for the nine months ended September 30, 2018 and 2017.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; margin-left: 36pt;"&gt;Research, development and patent expenses&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Long-lived assets&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We evaluate long-lived assets, which include property, plant and equipment 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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Use of estimates&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Basic and diluted net income (loss) per share&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Basic net income (loss) per share&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The calculation of total net income (loss) attributable to our common stockholders for the three and nine months ended September 30, 2018 and 2017 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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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; color: #000000;"&gt;September 30, 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 align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Three months ended September 30, 2018&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Weighted&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Average Shares&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Net Income (Loss)&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis&amp;#8217; Portion of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s Net Loss&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;65,538&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.73&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(47,843&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Akcea&amp;#8217;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(47,843&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Ionis&amp;#8217; stand-alone net income&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;43,226&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(4,616&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;143,314&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.03&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Akcea&amp;#8217;s net loss per share calculation for the nine months ended &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;September 30, 2018 included two components: (1) Akcea&amp;#8217;s net loss from its statement of operations and (2) deemed distributions related to the license of &lt;/font&gt;TEGSEDI in the second quarter of 2018. Because we own more than 50 percent of Akcea, we and Akcea are under common control.&amp;#160;As such, Akcea accounted for the TEGSEDI transaction using common control guidance.&amp;#160;Accordingly, Akcea recorded the license we granted to them at carrying value.&amp;#160;In addition, Akcea recorded the consideration it paid to us in excess of the carrying value as a deemed distribution.&amp;#160;Accounting rules required Akcea to include these deemed distributions in their net loss per share calculation as if Akcea had paid us a dividend. &amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Our basic net loss per share for the &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;nine months ended September 30, 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 align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Nine months ended September 30, 2018&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Weighted&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Average Shares&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Net Loss&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis&amp;#8217; Portion of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s Net Loss&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;57,347&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1.93&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(110,680&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Akcea&amp;#8217;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(110,680&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Ionis&amp;#8217; stand-alone net income&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;67,517&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(43,162&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;132,518&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.33&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Prior to Akcea&amp;#8217;s IPO in July 2017, we owned Akcea series A convertible preferred stock, which included a six percent cumulative dividend. Upon completion of Akcea&amp;#8217;s IPO in July 2017, our preferred stock was converted into common stock on a 1:1 basis. The preferred stock dividend was not paid at the IPO because the IPO was not a liquidation event or a change in control. During the three and nine months ended September 30, 2017, Akcea used a two-class method to compute its net income (loss) per share because it had both common and preferred shares outstanding during the periods. The two-class method required Akcea to calculate its net income (loss) per share&amp;#160;for each class of stock by dividing total distributable losses applicable to preferred and common stock, including the&amp;#160;six percent&amp;#160;cumulative dividend contractually due to series A convertible preferred shareholders, by the weighted-average of preferred and common shares outstanding during the requisite period. Since Akcea used the two-class method, accounting rules required us to include our portion of Akcea's net income (loss) per share for both Akcea's common and preferred shares that we owned in our calculation of basic and diluted net income (loss) per share for three and nine months ended September 30, 2017.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&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; color: #000000;"&gt;September 30, 2017&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 align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Three months ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Weighted&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Average Shares&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Net Loss&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis&amp;#8217; Portion of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s Net Loss&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;36,556&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.33&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(12,063&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Preferred shares&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5,651&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.01&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(57&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Akcea&amp;#8217;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(12,120&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Ionis&amp;#8217; stand-alone net income&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;10,144&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,976&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;124,370&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(0.02&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;Our basic net income per share for the &lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;nine months ended September 30, 2017&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 align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Nine months ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Weighted&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Average Shares&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Net Loss&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Ionis&amp;#8217; Portion of&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Akcea&amp;#8217;s Net Loss&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;12,319&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(3.12&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(38,435&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Preferred shares&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;21,055&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2.16&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(45,479&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Akcea&amp;#8217;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(83,914&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Ionis&amp;#8217; stand-alone net income&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;100,235&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16,321&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;123,746&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.13&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;Dilutive net income (loss per share)&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;For the three and nine months ended September 30, 2018 and for the three months ended September 30, 2017, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1 percent convertible senior notes;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;2&amp;#190; percent convertible senior notes;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Dilutive stock options;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Unvested restricted stock units; and&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 36pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;&amp;#9679;&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Employee Stock Purchase Plan, or ESPP.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;For the nine months ended September 30, 2017, 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 those periods. Diluted common equivalent shares for the nine months ended September 30, 2017 consisted of the following (in thousands except per share amounts):&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;Nine months ended September 30, 2017&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Income&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Shares&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Per-Share&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Amount&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16,321&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;123,746&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.13&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -8.9pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,658&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: 0.1pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;430&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; text-indent: 9.1pt;"&gt;Shares issuable related to our ESPP&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;24&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;"&gt;Income available to Ionis common stockholders, plus assumed conversions&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16,321&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;125,858&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;0.13&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;For the nine months ended September 30, 2017, the calculation excluded the 1 percent and 2&amp;#190; 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Accumulated other comprehensive loss&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We include unrealized gains and losses on investments, net of taxes, in accumulated other comprehensive income (loss) along with&amp;#160;adjustments we make to reclassify realized gains and losses on investments from other accumulated comprehensive income (loss) to our condensed consolidated statement of operations. The following table summarizes changes in accumulated other comprehensive income (loss) for the three and nine months ended September 30, 2018 and 2017 (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 90%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Beginning balance accumulated other comprehensive loss&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(32,637&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(30,372&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(31,759&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(30,358&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Unrealized gains (losses) on securities (1)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;133&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;215&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(834&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;610&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Amounts reclassified from accumulated other comprehensive loss&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(374&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Currency translation adjustment&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(28&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(42&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;61&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(77&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net current period other comprehensive income (loss)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;105&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;173&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(773&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;159&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Ending balance accumulated other comprehensive loss&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(32,532&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(30,199&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(32,532&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(30,199&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;(1)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;There was no income tax expense or benefit related to elements of other comprehensive income (loss) for the three and nine months ended September 30, 2018 and 2017.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Convertible debt&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Segment information&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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 drugs to treat patients with rare and serious diseases&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Stock-based compensation expense&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 nine months ended September 30, 2018 and 2017, 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; text-indent: 36pt;"&gt;Employee Stock Options:&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 60%; border-collapse: collapse;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;2.3%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;1.8%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;63.1%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;66.1%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;4.6 years&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;4.5 years&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&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; text-indent: 36pt;"&gt;Board of Director Stock Options:&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 60%; border-collapse: collapse;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;2.8 %&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;2.2 %&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0 %&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0 %&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;61.5 %&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;61.2 %&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;6.6 years&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;6.6 years&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;"&gt;ESPP:&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 60%; border-collapse: collapse;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;1.8%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.8%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;0.0%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;47.3%&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;59.9%&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;6 months&lt;/div&gt;&lt;/td&gt;&lt;td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;"&gt;6 months&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 and members of our board of directors for the nine months ended September 30, 2018 was $51.83 and $42.88 per share, respectively.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following table summarizes stock-based compensation expense for the three and nine months ended September 30, 2018 and 2017 (in thousands). Our consolidated non-cash stock-based compensation expense includes $12.7 million and $4.7 million of stock-based compensation expense for Akcea for the three months ended September 30, 2018 and 2017, respectively, and $31.2 million and $11.8 million for the nine months ended September 30, 2018 and 2017, respectively.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Research, development and patent&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;18,780&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16,181&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;57,698&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;48,443&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Selling, general and administrative&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16,103&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;5,291&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;39,512&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;15,199&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Total non-cash stock-based compensation expense&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;34,883&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;21,472&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;97,210&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;63,642&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;As of September 30, 2018, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options and RSUs was $139.5 million and $32.6 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 1.3 years and 1.6 years, respectively.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left; text-indent: 36pt;"&gt;Impact of recently issued accounting standards&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In February 2016, the FASB issued amended accounting guidance related to lease accounting, which will require us to record all leases with a term longer than one year on our balance sheet. When we record leases on our balance sheet under the new guidance, we will record a liability with a value equal to the present value of payments we will make over the life of the lease and an asset representing the underlying leased asset. The new accounting guidance requires us to determine if our leases are operating or financing leases. We will record expense for operating leases on a straight-line basis as an operating expense. If we determine a lease is a financing&amp;#160;lease, we will record both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. The new lease standard is effective for annual and interim periods beginning after December 15, 2018, with early adoption permitted. We will adopt this guidance on January 1, 2019. We can choose from two methods of adoption. The first method requires us to reflect our leases on our balance sheet in the earliest comparative period presented in our financial statements. The second method requires us to reflect the impact of adoption on the date we adopt the new guidance and recognize a cumulative-effect adjustment to the opening balance of our accumulated deficit in that period. We are currently determining the method we will use to adopt the new guidance and assessing the effects the new guidance will have on our consolidated financial statements and disclosures.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 consolidated financial statements and disclosures.&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In December 2017, the SEC staff issued guidance to address how companies should account for the Tax Act of 2017, or the Tax Act, when an entity does not have the necessary information to complete the accounting for the Tax Act and gives entities up to one year from the enactment of the Tax Act to finalize their amounts. We recognized provisional amounts in our 2017 financial statements and in these financial statements. The ultimate impact may differ materially from these provisional amounts due to, among other things, additional analysis, changes in our interpretations and assumptions, additional regulatory guidance that may be issued, and other actions we may take resulting from the Tax Act. We will assess and update our provisional amounts and disclosures, as necessary, at year end 2018.&lt;/div&gt;&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In February 2018, the FASB issued updated guidance for reclassification of tax effects from accumulated other comprehensive income (loss). The updated guidance gives entities an option to reclassify amounts included in accumulated other comprehensive income (loss) that under the Tax Act do not have a way to be relieved, and allows a one-time reclassification to retained earnings. The updated guidance is effective for all entities for fiscal years beginning after December 31, 2018, and interim periods within those fiscal years. Early adoption is permitted, and adoption is optional. We are currently assessing the effects this updated guidance could have on our consolidated financial statements and timing of potential adoption.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In June 2018, the FASB issued updated guidance to simplify the accounting for stock-based compensation expense for nonemployees. Specifically, we are now expensing grants to nonemployees in a similar manner as grants to employees and our Board of Directors. Previously, we had to re-value these grants at each reporting period to reflect the current fair value. Under the amended guidance, we value grants to nonemployees when we grant them and we will not adjust their value for future changes. We adopted this guidance in the second quarter of 2018 on a prospective basis. The updated guidance did not have a material impact to our financial results.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 consolidated financial statements and timing of adoption.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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 anticipate we will adopt this updated guidance on January 1, 2019 and we do not expect it to have a significant impact on our disclosures.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:SignificantAccountingPoliciesTextBlock>
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  <!--Stockholders' Equity, Policy [Policy Text Block]-->
  <us-gaap:StockholdersEquityPolicyTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Accumulated other comprehensive loss&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We include unrealized gains and losses on investments, net of taxes, in accumulated other comprehensive income (loss) along with&amp;#160;adjustments we make to reclassify realized gains and losses on investments from other accumulated comprehensive income (loss) to our condensed consolidated statement of operations. The following table summarizes changes in accumulated other comprehensive income (loss) for the three and nine months ended September 30, 2018 and 2017 (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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 90%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;"&gt;&amp;#160;&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2018&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;2017&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Beginning balance accumulated other comprehensive loss&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(32,637&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(30,372&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(31,759&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(30,358&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Unrealized gains (losses) on securities (1)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;133&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;215&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(834&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;610&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Amounts reclassified from accumulated other comprehensive loss&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(374&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Currency translation adjustment&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(28&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(42&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;61&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(77&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Net current period other comprehensive income (loss)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;105&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;173&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(773&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;159&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Ending balance accumulated other comprehensive loss&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(32,532&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(30,199&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(32,532&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(30,199&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&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;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;(1)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;There was no income tax expense or benefit related to elements of other comprehensive income (loss) for the three and nine months ended September 30, 2018 and 2017.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</us-gaap:StockholdersEquityPolicyTextBlock>
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  <!--Unrealized Gain (Loss) on Investments [Table Text Block]-->
  <us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;The following is a summary of our investments (in thousands):&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;br /&gt;&lt;/div&gt;&lt;table cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;September 30, 2018&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Cost &lt;/font&gt;(1)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Gains&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Losses&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Estimated Fair Value&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Available-for-sale securities:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Corporate debt securities (2)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;841,397&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;23&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,264&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;840,156&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;143,008&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;2&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(169&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;142,841&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Debt securities issued by the U.S. Treasury (2)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;154,280&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(89&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;154,191&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (2)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;49,873&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(330&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;49,543&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 4.5pt; text-indent: 13.5pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,188,558&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;25&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,852&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,186,731&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;240,208&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,420&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;238,804&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32,435&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(109&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;32,326&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;9,872&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(10&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;9,862&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;31,666&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(551&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;31,115&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 4.5pt; text-indent: 13.5pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;314,181&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;16&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2,090&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;312,107&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 4.5pt; text-indent: 22.5pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,502,739&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;41&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(3,942&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,498,838&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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;table cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;"&gt;December 31, 2017&lt;/div&gt;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: center;"&gt;&lt;font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Cost &lt;/font&gt;(1)&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Gains&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Losses&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 2px solid;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;"&gt;Estimated Fair Value&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="vertical-align: bottom;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Available-for-sale securities:&lt;/div&gt;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;td 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 nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;500,599&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;2&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(752&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;499,849&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;83,926&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(212&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;83,714&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;29,428&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(17&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;29,411&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (2)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;29,240&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;4&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(122&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;29,122&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;643,193&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;6&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,103&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;642,096&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;148,663&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,059&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;147,612&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;52,779&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(168&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;52,611&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,409&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(2&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;1,407&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;65,550&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;&amp;#8212;&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(740&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;64,810&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;268,401&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;8&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(1,969&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;266,440&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"&gt;&amp;#160;&lt;/td&gt;&lt;/tr&gt;&lt;tr&gt;&lt;td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;911,594&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;14&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;(3,072&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;)&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"&gt;&amp;#160;&lt;/td&gt;&lt;td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;$&lt;/div&gt;&lt;/td&gt;&lt;td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;908,536&lt;/div&gt;&lt;/td&gt;&lt;td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; 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: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;(1)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Our available-for-sale securities are held at amortized cost.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="text-align: left;"&gt;&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"&gt;&lt;tr&gt;&lt;td style="width: 18pt;"&gt;&lt;/td&gt;&lt;td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;"&gt;(2)&lt;/td&gt;&lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"&gt;Includes investments classified as cash equivalents on our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&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="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Use of estimates&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/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="c20170101to20170930" unitRef="U001" decimals="-3">123746000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
  <!--Shares used in computing basic net income (loss) per share (in shares)-->
  <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic contextRef="c20180701to20180930" unitRef="U001" decimals="-3">143314000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
  <!--Shares used in computing basic net income (loss) per share (in shares)-->
  <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic contextRef="c20180101to20180930" unitRef="U001" decimals="-3">132518000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
  <!--Shares used in computing basic net income (loss) per share (in shares)-->
  <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic contextRef="c20170701to20170930" unitRef="U001" decimals="-3">124370000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
  <!--Shares used in computing diluted net income (loss) per share (in shares)-->
  <us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding contextRef="c20180701to20180930" unitRef="U001" decimals="-3">143314000</us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding>
  <!--Shares used in computing diluted net income (loss) per share (in shares)-->
  <us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding contextRef="c20170101to20170930" unitRef="U001" decimals="-3">125858000</us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding>
  <!--Shares used in computing diluted net income (loss) per share (in shares)-->
  <us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding contextRef="c20170701to20170930" unitRef="U001" decimals="-3">124370000</us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding>
  <!--Shares used in computing diluted net income (loss) per share (in shares)-->
  <us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding contextRef="c20180101to20180930" unitRef="U001" decimals="-3">132518000</us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding>
  <!--Number of additional drugs in clinical development to treat neurodegenerative diseases-Collaborative Arrangements and Licensing Agreements, Biogen [Member]-->
  <ions:NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U010" decimals="INF">6</ions:NumberOfAdditionalDrugsInClinicalDevelopmentToTreatNeurodegenerativeDiseases>
  <!--Maximum amount of payments receivable per drug or program for development milestones-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]-->
  <ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-6">10000000</ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones>
  <!--Cumulative Revenue from Contract with Customer, Excluding Assessed Tax-Collaborative Arrangement and Licensing Agreement Entered Into in January 2012 with Biogen [Member]-Research and Development Revenue Under Collaborative Agreements [Member]-->
  <ions:CumulativeRevenueFromContractWithCustomerExcludingAssessedTax contextRef="c20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" unitRef="U002" decimals="-6">436000000</ions:CumulativeRevenueFromContractWithCustomerExcludingAssessedTax>
  <!--Cumulative Revenue from Contract with Customer, Excluding Assessed Tax-Collaborative Arrangement and Licensing Agreement Entered Into in January 2012 with Biogen [Member]-SPINRAZA Royalties [Member]-->
  <ions:CumulativeRevenueFromContractWithCustomerExcludingAssessedTax contextRef="c20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" unitRef="U002" decimals="-6">281000000</ions:CumulativeRevenueFromContractWithCustomerExcludingAssessedTax>
  <!--Cumulative Revenue from Contract with Customer, Excluding Assessed Tax-Collaborative Arrangement and Licensing Agreement Entered Into in January 2012 with Biogen [Member]-->
  <ions:CumulativeRevenueFromContractWithCustomerExcludingAssessedTax contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" unitRef="U002" decimals="-6">717000000</ions:CumulativeRevenueFromContractWithCustomerExcludingAssessedTax>
  <!--Number of drugs currently being advanced-Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]-->
  <ions:NumberOfDrugsCurrentlyBeingAdvanced contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U010" decimals="INF">5</ions:NumberOfDrugsCurrentlyBeingAdvanced>
  <!--Number of targets-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]-->
  <ions:NumberOfTargets contextRef="c20121231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U011" decimals="INF">3</ions:NumberOfTargets>
  <!--Maximum amount of payments receivable per drug or program for license fees and substantive milestone payments-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]-->
  <ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-6">210000000</ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments>
  <!--Maximum amount of payments receivable per drug or program for license fees and substantive milestone payments-Collaborative Arrangement and Licensing Agreement Entered Into in April 2018 with Biogen [Member]-->
  <ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U002" decimals="-6">270000000</ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments>
  <!--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>
  <!--Maximum amount of payments receivable for sales milestones-Collaborative Arrangement and Licensing Agreement Entered Into in December 2017 with Biogen [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForSalesMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U002" decimals="-6">800000000</ions:MaximumAmountOfPaymentsReceivableForSalesMilestones>
  <!--Percentage cash premium paid on shares purchased-Collaborative Arrangement and Licensing Agreement Entered Into in April 2018 with Biogen [Member]-->
  <ions:PercentageCashPremiumPaidOnSharesPurchased contextRef="c20180401to20180630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U003" decimals="INF">0.25</ions:PercentageCashPremiumPaidOnSharesPurchased>
  <!--Premium paid on shares purchased-Collaborative Arrangement and Licensing Agreement Entered Into in April 2018 with Biogen [Member]-->
  <ions:PremiumPaidOnSharesPurchased contextRef="c20180401to20180430_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U002" decimals="-6">177000000</ions:PremiumPaidOnSharesPurchased>
  <!--Term of collaboration agreement-Collaborative Arrangement and Licensing Agreement Entered Into in April 2018 with Biogen [Member]-->
  <ions:TermOfCollaborationAgreement contextRef="c20180101to20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember">P10Y</ions:TermOfCollaborationAgreement>
  <!--Number of programs under which drugs are to be developed and commercialized-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]-->
  <ions:NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized contextRef="c20121231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U012" decimals="INF">3</ions:NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized>
  <!--Number of programs under which drugs are to be developed and commercialized-Collaborative Arrangement and Licensing Agreement Entered Into in December 2014 with Janssen Biotech, Inc. [Member]-->
  <ions:NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized contextRef="c20141231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U012" decimals="INF">3</ions:NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized>
  <!--Royalty percentage received on net sales of drug-Collaborative Arrangement and Licensing Agreement Entered Into in December 2017 with Biogen [Member]-->
  <ions:RoyaltyPercentageReceivedOnNetSalesOfDrug contextRef="c20180101to20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U003" decimals="1">0.2</ions:RoyaltyPercentageReceivedOnNetSalesOfDrug>
  <!--Royalty percentage received on net sales of drug-Collaborative Arrangement and Licensing Agreement Entered Into in April 2018 with Biogen [Member]-->
  <ions:RoyaltyPercentageReceivedOnNetSalesOfDrug contextRef="c20180401to20180630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U003" decimals="1">0.2</ions:RoyaltyPercentageReceivedOnNetSalesOfDrug>
  <!--Royalty percentage received on net sales of drug-Minimum [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in January 2012 with Biogen [Member]-->
  <ions:RoyaltyPercentageReceivedOnNetSalesOfDrug contextRef="c20180101to20180930_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" unitRef="U003" decimals="INF">0.11</ions:RoyaltyPercentageReceivedOnNetSalesOfDrug>
  <!--Royalty percentage received on net sales of drug-Maximum [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in January 2012 with Biogen [Member]-->
  <ions:RoyaltyPercentageReceivedOnNetSalesOfDrug contextRef="c20180101to20180930_RangeAxis_MaximumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" unitRef="U003" decimals="INF">0.15</ions:RoyaltyPercentageReceivedOnNetSalesOfDrug>
  <!--Royalty percentage received on net sales of drug-Collaborative Arrangement and Licensing Agreement Entered Into in October 2018 with Roche [Member]-Subsequent Event [Member]-->
  <ions:RoyaltyPercentageReceivedOnNetSalesOfDrug contextRef="c20181001to20181031_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U003" decimals="1">0.2</ions:RoyaltyPercentageReceivedOnNetSalesOfDrug>
  <!--Maximum amount of payment receivable for each additional drug developed-Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]-->
  <ions:MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-5">136500000</ions:MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped>
  <!--Milestone payments received-Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]-->
  <ions:MilestonePaymentsReceived contextRef="c20161201to20161231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6">3000000</ions:MilestonePaymentsReceived>
  <!--Period to make interest only payments on mortgage loan-Primary Research and Development Facility [Member]-->
  <ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan contextRef="c20180101to20180930_PropertyPlantAndEquipmentByTypeAxis_PrimaryResearchAndDevelopmentFacilityMember">P5Y</ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan>
  <!--Period to make interest only payments on mortgage loan-Manufacturing Facility [Member]-->
  <ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan contextRef="c20180101to20180930_PropertyPlantAndEquipmentByTypeAxis_ManufacturingFacilityMember">P5Y</ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan>
  <!--Additional amount of common stock required to be purchased-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:AdditionalAmountOfCommonStockRequiredToBePurchased contextRef="c20170131_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6">50000000</ions:AdditionalAmountOfCommonStockRequiredToBePurchased>
  <!--Potential future premium-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
  <ions:PotentialFuturePremium contextRef="c20170131_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5">5000000</ions:PotentialFuturePremium>
  <!--Portion of upfront payment retained-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:PortionOfUpfrontPaymentRetained contextRef="c20170101to20170331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6">60000000</ions:PortionOfUpfrontPaymentRetained>
  <!--Portion of upfront payment paid as a sublicense fee-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:PortionOfUpfrontPaymentPaidAsASublicenseFee contextRef="c20170101to20170331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6">15000000</ions:PortionOfUpfrontPaymentPaidAsASublicenseFee>
  <!--Maximum amount of payments receivable for milestones-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-Akcea Therapeutics, Inc. [Member]-AKCEA-APO(a)-L [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForMilestones contextRef="c20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_ProductOrServiceAxis_AKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6">600000000</ions:MaximumAmountOfPaymentsReceivableForMilestones>
  <!--Maximum amount of payments receivable for milestones-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-Akcea Therapeutics, Inc. [Member]-AKCEA-APOCIII-L [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForMilestones contextRef="c20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_ProductOrServiceAxis_AKCEAAPOCIIILMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6">530000000</ions:MaximumAmountOfPaymentsReceivableForMilestones>
  <!--Royalty percentage received on sales of drug-Akcea Therapeutics, Inc. [Member]-AKCEA-APO(a)-L [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
  <ions:RoyaltyPercentageReceivedOnSalesOfDrug contextRef="c20180101to20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_ProductOrServiceAxis_AKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U003" decimals="1">0.2</ions:RoyaltyPercentageReceivedOnSalesOfDrug>
  <!--Royalty percentage received on sales of drug-AKCEA-APOCIII-L [Member]-Akcea Therapeutics, Inc. [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
  <ions:RoyaltyPercentageReceivedOnSalesOfDrug contextRef="c20180101to20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_ProductOrServiceAxis_AKCEAAPOCIIILMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U003" decimals="1">0.2</ions:RoyaltyPercentageReceivedOnSalesOfDrug>
  <!--Proceeds from sale of common stock, including premium paid-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
  <ions:ProceedsFromSaleOfCommonStockIncludingPremiumPaid contextRef="c20170101to20170331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6">100000000</ions:ProceedsFromSaleOfCommonStockIncludingPremiumPaid>
  <!--Percentage of license fees, milestone payments and royalties paid as sublicense fee-Akcea Therapeutics, Inc. [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
  <ions:PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee contextRef="c20180101to20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U003" decimals="INF">0.5</ions:PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee>
  <!--License fee receivable per drug-Akcea Therapeutics, Inc. [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
  <ions:LicenseFeePaidPerDrug contextRef="c20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6">150000000</ions:LicenseFeePaidPerDrug>
  <!--Potential premium received if common stock is purchased in the future-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
  <ions:PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture contextRef="c20170331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5">5000000</ions:PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture>
  <!--Premium received on shares issued-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
  <ions:PremiumReceivedOnSharesIssued contextRef="c20170101to20170331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5">28400000</ions:PremiumReceivedOnSharesIssued>
  <!--Number of drugs with exclusive option that could be exercised-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-Minimum [Member]-->
  <ions:NumberOfDrugsWithExclusiveOptionThatCouldBeExercised contextRef="c20170101to20170131_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U010" decimals="INF">1</ions:NumberOfDrugsWithExclusiveOptionThatCouldBeExercised>
  <!--Royalty percentage received on gross margins of drugs under collaboration agreement-Minimum [Member]-Collaborative Arrangements and Licensing Agreements, Bayer [Member]-->
  <ions:RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement contextRef="c20180101to20180930_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBayerMember" unitRef="U003" decimals="1">0.2</ions:RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement>
  <!--Payment received for advancing programs-Collaborative Arrangement and Licensing Agreement Amended in February 2017 with Bayer [Member]-->
  <ions:PaymentReceivedForAdvancingPrograms contextRef="c20170201to20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U002" decimals="-6">75000000</ions:PaymentReceivedForAdvancingPrograms>
  <!--Number of Significant Partners-Accounts Receivable [Member]-Significant Partners [Member]-Credit Concentration [Member]-->
  <ions:NumberOfSignificantPartners contextRef="c20170101to20171231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_SignificantPartnersMember" unitRef="U013" decimals="INF">2</ions:NumberOfSignificantPartners>
  <!--Number of Significant Partners-Significant Partners [Member]-Credit Concentration [Member]-Accounts Receivable [Member]-->
  <ions:NumberOfSignificantPartners contextRef="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_SignificantPartnersMember" unitRef="U013" decimals="INF">2</ions:NumberOfSignificantPartners>
  <!--Term of variable rate-Revolving Line of Credit [Member]-Morgan Stanley Private Bank, National Association [Member]-LIBOR [Member]-->
  <ions:TermOfVariableRate contextRef="c20180101to20180930_CreditFacilityAxis_RevolvingCreditFacilityMember_LineOfCreditFacilityAxis_MorganStanleyPrivateBankNationalAssociationMember_VariableRateAxis_LondonInterbankOfferedRateLIBORMember">P1M</ions:TermOfVariableRate>
  <!--Weighted average number of shares owned in subsidiary-Akcea Therapeutics, Inc. [Member]-Common Stock [Member]-->
  <ions:WeightedAverageNumberOfSharesOwnedInSubsidiary contextRef="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-3">65538000</ions:WeightedAverageNumberOfSharesOwnedInSubsidiary>
  <!--Weighted average number of shares owned in subsidiary-Akcea Therapeutics, Inc. [Member]-Common Stock [Member]-->
  <ions:WeightedAverageNumberOfSharesOwnedInSubsidiary contextRef="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-3">57347000</ions:WeightedAverageNumberOfSharesOwnedInSubsidiary>
  <!--Weighted average number of shares owned in subsidiary-Convertible Preferred Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:WeightedAverageNumberOfSharesOwnedInSubsidiary contextRef="c20170101to20170930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_ConvertiblePreferredStockMember" unitRef="U001" decimals="-3">21055000</ions:WeightedAverageNumberOfSharesOwnedInSubsidiary>
  <!--Weighted average number of shares owned in subsidiary-Common Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:WeightedAverageNumberOfSharesOwnedInSubsidiary contextRef="c20170101to20170930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-3">12319000</ions:WeightedAverageNumberOfSharesOwnedInSubsidiary>
  <!--Weighted average number of shares owned in subsidiary-Common Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:WeightedAverageNumberOfSharesOwnedInSubsidiary contextRef="c20170701to20170930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-3">36556000</ions:WeightedAverageNumberOfSharesOwnedInSubsidiary>
  <!--Weighted average number of shares owned in subsidiary-Convertible Preferred Stock [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:WeightedAverageNumberOfSharesOwnedInSubsidiary contextRef="c20170701to20170930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_ConvertiblePreferredStockMember" unitRef="U001" decimals="-3">5651000</ions:WeightedAverageNumberOfSharesOwnedInSubsidiary>
  <!--Incremental Common Shares Attributable to Employee Stock Purchase Plan-->
  <ions:IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan contextRef="c20170101to20170930" unitRef="U001" decimals="-3">24000</ions:IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan>
  <!--Receipt of shares in subsidiary-Akcea Therapeutics, Inc. [Member]-Subsequent Event [Member]-->
  <ions:ReceiptOfSharesInSubsidiary contextRef="c20181001to20181031_OwnershipAxis_AkceaTherapeuticsIncMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U001" decimals="-5">1700000</ions:ReceiptOfSharesInSubsidiary>
  <!--Number of antisense drugs in development-Collaborative Arrangement and Licensing Agreement Entered Into in March 2010 with GSK [Member]-->
  <ions:NumberOfAntisenseDrugsInDevelopment contextRef="c20180101to20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U010" decimals="INF">2</ions:NumberOfAntisenseDrugsInDevelopment>
  <!--Maximum amount of payments receivable for license fees and substantive milestones-Antisense Molecule [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones contextRef="c20180930_ProductOrServiceAxis_AntisenseMoleculeMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6">260000000</ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones>
  <!--Maximum amount of payments receivable for license fees and substantive milestones-Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]-Other Modalities [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones contextRef="c20180930_ProductOrServiceAxis_OtherModalitiesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6">90000000</ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones>
  <!--Maximum amount of payments receivable for license fees and substantive milestones-Collaborative Arrangement and Licensing Agreement Entered Into in December 2017 with Biogen [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U002" decimals="-8">1200000000</ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones>
  <!--Maximum amount of payments receivable for license fees and substantive milestones-Collaborative Arrangements and Licensing Agreements, Bayer [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBayerMember" unitRef="U002" decimals="-6">385000000</ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones>
  <!--Maximum amount of payments receivable for license fees and substantive milestones-Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6">365000000</ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones>
  <!--Maximum amount of payments receivable for license fees and substantive milestones-Collaborative Arrangement and Licensing Agreement Entered Into in October 2018 with Roche [Member]-Subsequent Event [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones contextRef="c20181031_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U002" decimals="-6">684000000</ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones>
  <!--Maximum amount of payments receivable for license fees and substantive milestones-Collaborative Arrangement and Licensing Agreement Entered Into in March 2010 with GSK [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-6">262000000</ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones>
  <!--Next potential milestone payment-Collaborative Arrangements and Licensing Agreements, Bayer [Member]-->
  <ions:NextPotentialMilestonePayment contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBayerMember" unitRef="U002" decimals="-6">10000000</ions:NextPotentialMilestonePayment>
  <!--Next potential milestone payment-Collaborative Arrangement and Licensing Agreement Entered Into in December 2014 with Janssen Biotech, Inc. [Member]-->
  <ions:NextPotentialMilestonePayment contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U002" decimals="-6">5000000</ions:NextPotentialMilestonePayment>
  <!--Next potential milestone payment-Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]-->
  <ions:NextPotentialMilestonePayment contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6">35000000</ions:NextPotentialMilestonePayment>
  <!--Next potential milestone payment-Collaborative Arrangement and Licensing Agreement Entered Into in October 2018 with Roche [Member]-Subsequent Event [Member]-->
  <ions:NextPotentialMilestonePayment contextRef="c20181031_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U002" decimals="-6">20000000</ions:NextPotentialMilestonePayment>
  <!--Next potential milestone payment-Collaborative Arrangement and Licensing Agreement Entered Into in March 2010 with GSK [Member]-Maximum [Member]-->
  <ions:NextPotentialMilestonePayment contextRef="c20180930_RangeAxis_MaximumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-6">25000000</ions:NextPotentialMilestonePayment>
  <!--Maximum amount of payments receivable for commercialization milestones-Collaborative Arrangement and Licensing Agreement Entered Into in December 2017 with Biogen [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U002" decimals="-6">180000000</ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones>
  <!--Maximum amount of payments receivable for commercialization milestones-Collaborative Arrangements and Licensing Agreements, Bayer [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBayerMember" unitRef="U002" decimals="-6">110000000</ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones>
  <!--Maximum amount of payments receivable for commercialization milestones-Collaborative Arrangement and Licensing Agreement Entered Into in December 2014 with Janssen Biotech, Inc. [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U002" decimals="-6">180000000</ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones>
  <!--Maximum amount of payments receivable for commercialization milestones-Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6">80000000</ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones>
  <!--Maximum amount of payments receivable for commercialization milestones-Collaborative Arrangement and Licensing Agreement Entered Into in March 2010 with GSK [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-6">70000000</ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones>
  <!--Maximum amount of payments receivable for commercialization milestones-AKCEA-APOCIII-L [Member]-Akcea Therapeutics, Inc. [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones contextRef="c20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_ProductOrServiceAxis_AKCEAAPOCIIILMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6">265000000</ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones>
  <!--Maximum amount of payments receivable for commercialization milestones-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-AKCEA-APO(a)-L [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones contextRef="c20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_ProductOrServiceAxis_AKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6">285000000</ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones>
  <!--Milestone payment earned and amortized over period of performance-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]-->
  <ions:MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance contextRef="c20170701to20170930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-6">10000000</ions:MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance>
  <!--Period after billing when payment is received-->
  <ions:PeriodAfterBillingWhenPaymentIsReceived contextRef="c20180101to20180930">P3M</ions:PeriodAfterBillingWhenPaymentIsReceived>
  <!--Number of agreements with collaboration partner-Biogen Inc. [Member]-->
  <ions:NumberOfAgreementsWithCollaborationPartner contextRef="c20180401to20180630_MajorCustomersAxis_BiogenIncMember" unitRef="U006" decimals="INF">2</ions:NumberOfAgreementsWithCollaborationPartner>
  <!--Royalty percentage received on net sales of each drug in Latin America from collaboration partner-Collaborative Arrangement and Licensing Agreement Entered Into in August 2018 with PTC Therapeutics [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner contextRef="c20180701to20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember" unitRef="U003" decimals="1">0.2</ions:RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner>
  <!--Period before collaboration partner pays royalties on net sales of product after first commercial sale in Brazil-Collaborative Arrangement and Licensing Agreement Entered Into in August 2018 with PTC Therapeutics [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil contextRef="c20180101to20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember">P12M</ions:PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil>
  <!--Revenue recognized by collaboration partner in Latin America before paying royalties-Collaborative Arrangement and Licensing Agreement Entered Into in August 2018 with PTC Therapeutics [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties contextRef="c20180701to20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember" unitRef="U002" decimals="-6">10000000</ions:RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties>
  <!--Payment receivable under license agreement to be paid after approval-Collaborative Arrangement and Licensing Agreement Entered Into in August 2018 with PTC Therapeutics [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval contextRef="c20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember" unitRef="U002" decimals="-6">6000000</ions:PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval>
  <!--Maximum amount of payments receivable per drug or program for regulatory milestones-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]-->
  <ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-6">130000000</ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones>
  <!--Maximum amount of payments receivable per drug or program for regulatory milestones-Akcea Therapeutics, Inc. [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in August 2018 with PTC Therapeutics [Member]-->
  <ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones contextRef="c20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember" unitRef="U002" decimals="-6">8000000</ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones>
  <!--Payment receivable under license agreement-Collaborative Arrangement and Licensing Agreement Entered Into in August 2018 with PTC Therapeutics [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:PaymentReceivableUnderLicenseAgreement contextRef="c20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember" unitRef="U002" decimals="-6">26000000</ions:PaymentReceivableUnderLicenseAgreement>
  <!--Payment to settle financing liability for leased facility-->
  <ions:PaymentToSettleFinancingLiabilityForLeasedFacility contextRef="c20180101to20180930" unitRef="U002" decimals="-3">0</ions:PaymentToSettleFinancingLiabilityForLeasedFacility>
  <!--Payment to settle financing liability for leased facility-->
  <ions:PaymentToSettleFinancingLiabilityForLeasedFacility contextRef="c20170101to20170930" unitRef="U002" decimals="-3">80133000</ions:PaymentToSettleFinancingLiabilityForLeasedFacility>
  <!--Amortization of Patents-->
  <ions:AmortizationOfPatents contextRef="c20170101to20170930" unitRef="U002" decimals="-3">1216000</ions:AmortizationOfPatents>
  <!--Amortization of Patents-->
  <ions:AmortizationOfPatents contextRef="c20180101to20180930" unitRef="U002" decimals="-3">1356000</ions:AmortizationOfPatents>
  <!--Gain (Loss) on Available-for-Sale Equity Securities, Significant Investment-->
  <ions:GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment contextRef="c20170101to20170930" unitRef="U002" decimals="-3">374000</ions:GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment>
  <!--Gain (Loss) on Available-for-Sale Equity Securities, Significant Investment-->
  <ions:GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment contextRef="c20180101to20180930" unitRef="U002" decimals="-3">0</ions:GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment>
  <!--Payments to Acquire Licenses and Other Assets-->
  <ions:PaymentsToAcquireLicensesAndOtherAssets contextRef="c20170101to20170930" unitRef="U002" decimals="-3">4289000</ions:PaymentsToAcquireLicensesAndOtherAssets>
  <!--Payments to Acquire Licenses and Other Assets-->
  <ions:PaymentsToAcquireLicensesAndOtherAssets contextRef="c20180101to20180930" unitRef="U002" decimals="-3">3317000</ions:PaymentsToAcquireLicensesAndOtherAssets>
  <!--Increase (Decrease) in Accrued and Deferred Liabilities-->
  <ions:IncreaseDecreaseInAccruedAndDeferredLiabilities contextRef="c20170101to20170930" unitRef="U002" decimals="-3">-5251000</ions:IncreaseDecreaseInAccruedAndDeferredLiabilities>
  <!--Increase (Decrease) in Accrued and Deferred Liabilities-->
  <ions:IncreaseDecreaseInAccruedAndDeferredLiabilities contextRef="c20180101to20180930" unitRef="U002" decimals="-3">-14392000</ions:IncreaseDecreaseInAccruedAndDeferredLiabilities>
  <!--Unpaid Deferred Offering Costs-->
  <ions:UnpaidDeferredOfferingCosts contextRef="c20170101to20170930" unitRef="U002" decimals="-3">638000</ions:UnpaidDeferredOfferingCosts>
  <!--Unpaid Deferred Offering Costs-->
  <ions:UnpaidDeferredOfferingCosts contextRef="c20180101to20180930" unitRef="U002" decimals="-3">0</ions:UnpaidDeferredOfferingCosts>
  <!--Non-cash Capital and Patent Expenditures-->
  <ions:NonCashCapitalAndPatentExpenditures contextRef="c20180101to20180930" unitRef="U002" decimals="-3">2296000</ions:NonCashCapitalAndPatentExpenditures>
  <!--Non-cash Capital and Patent Expenditures-->
  <ions:NonCashCapitalAndPatentExpenditures contextRef="c20170101to20170930" unitRef="U002" decimals="-3">3475000</ions:NonCashCapitalAndPatentExpenditures>
  <!--Gain (Loss) on Extinguishment of Financing Liability-->
  <ions:GainLossOnExtinguishmentOfFinancingLiability contextRef="c20170101to20170930" unitRef="U002" decimals="-3">-7689000</ions:GainLossOnExtinguishmentOfFinancingLiability>
  <!--Gain (Loss) on Extinguishment of Financing Liability-->
  <ions:GainLossOnExtinguishmentOfFinancingLiability contextRef="c20170701to20170930" unitRef="U002" decimals="-3">-7689000</ions:GainLossOnExtinguishmentOfFinancingLiability>
  <!--Gain (Loss) on Extinguishment of Financing Liability-->
  <ions:GainLossOnExtinguishmentOfFinancingLiability contextRef="c20180701to20180930" unitRef="U002" decimals="-3">0</ions:GainLossOnExtinguishmentOfFinancingLiability>
  <!--Gain (Loss) on Extinguishment of Financing Liability-->
  <ions:GainLossOnExtinguishmentOfFinancingLiability contextRef="c20180101to20180930" unitRef="U002" decimals="-3">0</ions:GainLossOnExtinguishmentOfFinancingLiability>
  <!--Research Development and Patent Expense-->
  <ions:ResearchDevelopmentAndPatentExpense contextRef="c20170101to20170930" unitRef="U002" decimals="-3">246358000</ions:ResearchDevelopmentAndPatentExpense>
  <!--Research Development and Patent Expense-->
  <ions:ResearchDevelopmentAndPatentExpense contextRef="c20180701to20180930" unitRef="U002" decimals="-3">95255000</ions:ResearchDevelopmentAndPatentExpense>
  <!--Research Development and Patent Expense-->
  <ions:ResearchDevelopmentAndPatentExpense contextRef="c20170701to20170930" unitRef="U002" decimals="-3">80214000</ions:ResearchDevelopmentAndPatentExpense>
  <!--Research Development and Patent Expense-->
  <ions:ResearchDevelopmentAndPatentExpense contextRef="c20180101to20180930" unitRef="U002" decimals="-3">301153000</ions:ResearchDevelopmentAndPatentExpense>
  <!--Maximum contract maturity period, range 3-->
  <ions:MaximumContractMaturityPeriodRange3 contextRef="c20180101to20180930">P3Y</ions:MaximumContractMaturityPeriodRange3>
  <!--Maximum contract maturity period, range 2-->
  <ions:MaximumContractMaturityPeriodRange2 contextRef="c20180101to20180930">P2Y</ions:MaximumContractMaturityPeriodRange2>
  <!--Maximum contract maturity period, range 1-->
  <ions:MaximumContractMaturityPeriodRange1 contextRef="c20180101to20180930">P1Y</ions:MaximumContractMaturityPeriodRange1>
  <!--Available-for-sale Securities, Debt Maturities, after Two Through Three Years, Percentage-->
  <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage contextRef="c20180930" unitRef="U003" decimals="2">0.05</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage>
  <!--Available-for-sale Securities, Debt Maturities, after One Through Two Years, Percentage-->
  <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage contextRef="c20180930" unitRef="U003" decimals="2">0.15</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage>
  <!--Available-for-sale Securities, Debt Maturities, Total, Percentage-->
  <ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage contextRef="c20180930" unitRef="U003" decimals="INF">1</ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage>
  <!--Available-for-sale Securities, Debt Maturities, within Two Years, Percentage-->
  <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage contextRef="c20180930" unitRef="U003" decimals="2">0.95</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage>
  <!--Available-for-sale Securities, Debt Maturities, within One Year, Percentage-->
  <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage contextRef="c20180930" unitRef="U003" decimals="1">0.8</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage>
  <!--Number of Publicly-Held Companies in which Entity has Equity Investment-->
  <ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment contextRef="c20180930" unitRef="U007" decimals="INF">1</ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment>
  <!--Number of Privately-Held Companies in which Entity has Equity Investment-->
  <ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment contextRef="c20180930" unitRef="U007" decimals="INF">4</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
  <!--New Accounting Pronouncement or Change in Accounting Principle, Effect of Change on Revenue from amortization of milestone payments achieved under new revenue guidance-->
  <ions:NewAccountingPronouncementOrChangeInAccountingPrincipleEffectOfChangeOnRevenueFromAmortizationOfMilestonePaymentsAchievedUnderNewRevenueGuidance contextRef="c20170701to20170930" unitRef="U002" decimals="-5">500000</ions:NewAccountingPronouncementOrChangeInAccountingPrincipleEffectOfChangeOnRevenueFromAmortizationOfMilestonePaymentsAchievedUnderNewRevenueGuidance>
  <!--New Accounting Pronouncement or Change in Accounting Principle, Effect of Change on Revenue from amortization of milestone payments achieved under new revenue guidance-->
  <ions:NewAccountingPronouncementOrChangeInAccountingPrincipleEffectOfChangeOnRevenueFromAmortizationOfMilestonePaymentsAchievedUnderNewRevenueGuidance contextRef="c20170101to20170930" unitRef="U002" decimals="-5">27900000</ions:NewAccountingPronouncementOrChangeInAccountingPrincipleEffectOfChangeOnRevenueFromAmortizationOfMilestonePaymentsAchievedUnderNewRevenueGuidance>
  <!--New Accounting Pronouncement or Change in Accounting Principle, Effect of Change on Revenue from amortization of payments using input method-->
  <ions:NewAccountingPronouncementOrChangeInAccountingPrincipleEffectOfChangeOnRevenueFromAmortizationOfPaymentsUsingInputMethod contextRef="c20170701to20170930" unitRef="U002" decimals="-5">-4000000</ions:NewAccountingPronouncementOrChangeInAccountingPrincipleEffectOfChangeOnRevenueFromAmortizationOfPaymentsUsingInputMethod>
  <!--New Accounting Pronouncement or Change in Accounting Principle, Effect of Change on Revenue from amortization of payments using input method-->
  <ions:NewAccountingPronouncementOrChangeInAccountingPrincipleEffectOfChangeOnRevenueFromAmortizationOfPaymentsUsingInputMethod contextRef="c20170101to20170930" unitRef="U002" decimals="-5">-17500000</ions:NewAccountingPronouncementOrChangeInAccountingPrincipleEffectOfChangeOnRevenueFromAmortizationOfPaymentsUsingInputMethod>
  <!--Cash, Cash Equivalents and Investments [Policy Text Block]-->
  <ions:CashCashEquivalentsAndInvestmentsPolicyTextBlock contextRef="c20180101to20180930">&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;"&gt;Cash, cash equivalents and investments&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At September 30, 2018, we held an equity investment in one publicly held company, 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;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"&gt;In January 2018, we adopted the amended accounting guidance related to the recognition, measurement, presentation, and disclosure of certain financial instruments. The amended guidance requires us to measure and record our equity investments at fair value. Additionally, the amended accounting guidance requires us to recognize the changes in fair value in our consolidated statement of operations, instead of through accumulated other comprehensive income. Prior to 2018, we accounted for our equity investments in privately held companies under the cost method of accounting. Under the amended guidance we account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. Our adoption of this guidance did not have an impact on our results.&lt;/div&gt;&lt;div&gt;&lt;br /&gt;&lt;/div&gt;&lt;/div&gt;</ions:CashCashEquivalentsAndInvestmentsPolicyTextBlock>
  <!--Long-term Obligations, Current-->
  <ions:LongTermObligationsCurrent contextRef="c20171231" unitRef="U002" decimals="-3">1621000</ions:LongTermObligationsCurrent>
  <!--Long-term Obligations, Current-->
  <ions:LongTermObligationsCurrent contextRef="c20180930" unitRef="U002" decimals="-3">14472000</ions:LongTermObligationsCurrent>
  <!--Long-term Obligations, Noncurrent-->
  <ions:LongTermObligationsNoncurrent contextRef="c20171231" unitRef="U002" decimals="-3">12974000</ions:LongTermObligationsNoncurrent>
  <!--Long-term Obligations, Noncurrent-->
  <ions:LongTermObligationsNoncurrent contextRef="c20180930" unitRef="U002" decimals="-3">5138000</ions:LongTermObligationsNoncurrent>
  <!--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 separate performance obligations-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]-->
  <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations contextRef="c20121231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U005" decimals="INF">1</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
  <!--Revenue from Contract with Customer, Number of separate performance obligations-Collaborative Arrangement and Licensing Agreement Entered Into in December 2017 with Biogen [Member]-->
  <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations contextRef="c20171231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U005" decimals="INF">1</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
  <!--Revenue from Contract with Customer, Number of separate performance obligations-Collaborative Arrangement and Licensing Agreement Entered Into in April 2018 with Biogen [Member]-->
  <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations contextRef="c20180430_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U005" decimals="INF">1</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
  <!--Revenue from Contract with Customer, Number of separate performance obligations-Collaborative Arrangement and Licensing Agreement Entered Into in January 2012 with Biogen [Member]-->
  <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations contextRef="c20161231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" unitRef="U005" decimals="INF">2</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
  <!--Revenue from Contract with Customer, Number of separate performance obligations-Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]-->
  <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations contextRef="c20130930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U005" decimals="INF">1</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
  <!--Revenue from Contract with Customer, Number of separate performance obligations-Collaborative Arrangement and Licensing Agreement Entered Into in July 2015 with AstraZeneca [Member]-->
  <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations contextRef="c20150731_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstraZenecaMember" unitRef="U005" decimals="INF">1</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
  <!--Revenue from Contract with Customer, Number of separate performance obligations-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with AstraZeneca [Member]-->
  <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations contextRef="c20121231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstraZenecaMember" unitRef="U005" decimals="INF">4</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
  <!--Revenue from Contract with Customer, Number of separate performance obligations-Collaborative Arrangement and Licensing Agreement Entered Into in May 2015 with Bayer [Member]-->
  <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations contextRef="c20150531_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U005" decimals="INF">3</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
  <!--Revenue from Contract with Customer, Number of separate performance obligations-Collaborative Arrangement and Licensing Agreement Amended in February 2017 with Bayer [Member]-->
  <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations contextRef="c20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U005" decimals="INF">2</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
  <!--Revenue from Contract with Customer, Number of separate performance obligations-Collaborative Arrangement and Licensing Agreement Entered Into in December 2014 with Janssen Biotech, Inc. [Member]-->
  <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations contextRef="c20141231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U005" decimals="INF">1</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
  <!--Revenue from Contract with Customer, Number of separate performance obligations-Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]-->
  <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations contextRef="c20130430_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U005" decimals="INF">1</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
  <!--Revenue from Contract with Customer, Number of separate performance obligations-Collaborative Arrangement and Licensing Agreement Entered Into in March 2010 with GSK [Member]-->
  <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations contextRef="c20100331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U005" decimals="INF">1</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
  <!--Revenue from Contract with Customer, Number of separate performance obligations-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
  <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations contextRef="c20170331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U005" decimals="INF">4</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
  <!--Revenue from Contract with Customer, Number of separate performance obligations-Collaborative Arrangement and Licensing Agreement Entered Into in August 2018 with PTC Therapeutics [Member]-->
  <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations contextRef="c20180831_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember" unitRef="U005" decimals="INF">2</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
  <!--Payments included in transaction price for performance obligation-Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]-Research and Development Revenue Under Collaborative Agreements [Member]-->
  <ions:PaymentsIncludedInTransactionPriceForPerformanceObligation contextRef="c20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6">145000000</ions:PaymentsIncludedInTransactionPriceForPerformanceObligation>
  <!--Payments included in transaction price for performance obligation-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]-Research and Development Revenue Under Collaborative Agreements [Member]-->
  <ions:PaymentsIncludedInTransactionPriceForPerformanceObligation contextRef="c20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-6">40000000</ions:PaymentsIncludedInTransactionPriceForPerformanceObligation>
  <!--Payments included in transaction price for performance obligation-Collaborative Arrangement and Licensing Agreement Entered Into in July 2015 with AstraZeneca [Member]-Research and Development Revenue Under Collaborative Agreements [Member]-->
  <ions:PaymentsIncludedInTransactionPriceForPerformanceObligation contextRef="c20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstraZenecaMember" unitRef="U002" decimals="-6">90000000</ions:PaymentsIncludedInTransactionPriceForPerformanceObligation>
  <!--Maximum amount of payments receivable for regulatory milestones-Other Modalities [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones contextRef="c20180930_ProductOrServiceAxis_OtherModalitiesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6">55000000</ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones>
  <!--Maximum amount of payments receivable for regulatory milestones-Antisense Molecule [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones contextRef="c20180930_ProductOrServiceAxis_AntisenseMoleculeMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6">130000000</ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones>
  <!--Maximum amount of payments receivable for regulatory milestones-Collaborative Arrangement and Licensing Agreement Entered Into in July 2015 with AstraZeneca [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstraZenecaMember" unitRef="U002" decimals="-8">2900000000</ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones>
  <!--Maximum amount of payments receivable for regulatory milestones-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with AstraZeneca [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstraZenecaMember" unitRef="U002" decimals="-6">275000000</ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones>
  <!--Maximum amount of payments receivable for regulatory milestones-Collaborative Arrangement and Licensing Agreement Entered Into in December 2014 with Janssen Biotech, Inc. [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U002" decimals="-6">440000000</ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones>
  <!--Maximum amount of payments receivable for regulatory milestones-Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6">170000000</ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones>
  <!--Maximum amount of payments receivable for regulatory milestones-Collaborative Arrangement and Licensing Agreement Entered Into in March 2010 with GSK [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-6">120000000</ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones>
  <!--Maximum amount of payments receivable for regulatory milestones-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-AKCEA-APOCIII-L [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones contextRef="c20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_ProductOrServiceAxis_AKCEAAPOCIIILMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6">240000000</ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones>
  <!--Maximum amount of payments receivable for regulatory milestones-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-AKCEA-APO(a)-L [Member]-Akcea Therapeutics, Inc. [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones contextRef="c20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_ProductOrServiceAxis_AKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6">290000000</ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones>
  <!--Minimum amount of payments receivable for license fees and substantive milestones-Collaborative Arrangement and Licensing Agreement Entered Into in July 2015 with AstraZeneca [Member]-->
  <ions:MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstraZenecaMember" unitRef="U002" decimals="-9">4000000000</ions:MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones>
  <!--Minimum amount of payments receivable for license fees and substantive milestones-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with AstraZeneca [Member]-->
  <ions:MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstraZenecaMember" unitRef="U002" decimals="-6">450000000</ions:MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones>
  <!--Minimum amount of payments receivable for license fees and substantive milestones-Collaborative Arrangement and Licensing Agreement Entered Into in December 2014 with Janssen Biotech, Inc. [Member]-->
  <ions:MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U002" decimals="-6">800000000</ions:MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones>
  <!--Maximum amount of payments receivable for development milestones-Collaborative Arrangement and Licensing Agreement Entered Into in December 2017 with Biogen [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U002" decimals="-6">80000000</ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones>
  <!--Maximum amount of payments receivable for development milestones-Antisense Molecule [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones contextRef="c20180930_ProductOrServiceAxis_AntisenseMoleculeMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6">60000000</ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones>
  <!--Maximum amount of payments receivable for development milestones-Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]-Other Modalities [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones contextRef="c20180930_ProductOrServiceAxis_OtherModalitiesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6">35000000</ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones>
  <!--Maximum amount of payments receivable for development milestones-Collaborative Arrangement and Licensing Agreement Entered Into in July 2015 with AstraZeneca [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstraZenecaMember" unitRef="U002" decimals="-8">1100000000</ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones>
  <!--Maximum amount of payments receivable for development milestones-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with AstraZeneca [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstraZenecaMember" unitRef="U002" decimals="-6">152000000</ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones>
  <!--Maximum amount of payments receivable for development milestones-Collaborative Arrangements and Licensing Agreements, Bayer [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBayerMember" unitRef="U002" decimals="-6">125000000</ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones>
  <!--Maximum amount of payments receivable for development milestones-Collaborative Arrangement and Licensing Agreement Entered Into in December 2014 with Janssen Biotech, Inc. [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U002" decimals="-6">175000000</ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones>
  <!--Maximum amount of payments receivable for development milestones-Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6">70000000</ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones>
  <!--Maximum amount of payments receivable for development milestones-Collaborative Arrangement and Licensing Agreement Entered Into in March 2010 with GSK [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-5">47500000</ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones>
  <!--Maximum amount of payments receivable for development milestones-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-Akcea Therapeutics, Inc. [Member]-AKCEA-APOCIII-L [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones contextRef="c20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_ProductOrServiceAxis_AKCEAAPOCIIILMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6">25000000</ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones>
  <!--Maximum amount of payments receivable for development milestones-Akcea Therapeutics, Inc. [Member]-AKCEA-APO(a)-L [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
  <ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones contextRef="c20180930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_ProductOrServiceAxis_AKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6">25000000</ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones>
  <!--Cumulative payments received-Collaborative Arrangements and Licensing Agreements, Biogen [Member]-->
  <ions:CumulativePaymentsReceived contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-8">1900000000</ions:CumulativePaymentsReceived>
  <!--Cumulative payments received-Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]-->
  <ions:CumulativePaymentsReceived contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6">170000000</ions:CumulativePaymentsReceived>
  <!--Cumulative payments received-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]-->
  <ions:CumulativePaymentsReceived contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-6">58000000</ions:CumulativePaymentsReceived>
  <!--Cumulative payments received-Collaborative Arrangement and Licensing Agreement Entered Into in July 2015 with AstraZeneca [Member]-->
  <ions:CumulativePaymentsReceived contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstraZenecaMember" unitRef="U002" decimals="-6">165000000</ions:CumulativePaymentsReceived>
  <!--Cumulative payments received-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with AstraZeneca [Member]-->
  <ions:CumulativePaymentsReceived contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstraZenecaMember" unitRef="U002" decimals="-5">97800000</ions:CumulativePaymentsReceived>
  <!--Cumulative payments received-Collaborative Arrangements and Licensing Agreements, Bayer [Member]-->
  <ions:CumulativePaymentsReceived contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBayerMember" unitRef="U002" decimals="-6">175000000</ions:CumulativePaymentsReceived>
  <!--Cumulative payments received-Collaborative Arrangement and Licensing Agreement Entered Into in December 2014 with Janssen Biotech, Inc. [Member]-->
  <ions:CumulativePaymentsReceived contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U002" decimals="-6">75000000</ions:CumulativePaymentsReceived>
  <!--Cumulative payments received-Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]-->
  <ions:CumulativePaymentsReceived contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6">110000000</ions:CumulativePaymentsReceived>
  <!--Cumulative payments received-Minimum [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in March 2010 with GSK [Member]-->
  <ions:CumulativePaymentsReceived contextRef="c20180930_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-6">162000000</ions:CumulativePaymentsReceived>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in April 2018 with Biogen [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20180430_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U002" decimals="-6">552000000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in December 2017 with Biogen [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20171231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U002" decimals="-6">25000000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20130930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6">100000000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20121231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-6">30000000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with AstraZeneca [Member]-Research and Development Revenue Under Collaborative Agreements [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20121231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstraZenecaMember" unitRef="U002" decimals="-5">7600000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with AstraZeneca [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20121231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstraZenecaMember" unitRef="U002" decimals="-6">31000000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in July 2015 with AstraZeneca [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20150731_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstraZenecaMember" unitRef="U002" decimals="-6">65000000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-IONIS-FXI [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in May 2015 with Bayer [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20150531_ProductOrServiceAxis_IONISFXIMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U002" decimals="-5">91200000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in May 2015 with Bayer [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20150531_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U002" decimals="-6">100000000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--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>
  <!--Revenue from Contract with Customer, Transaction Price-Research and Development Services for IONIS-FXI-L [Member]-Collaborative Arrangement and Licensing Agreement Amended in February 2017 with Bayer [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20170228_ProductOrServiceAxis_ResearchAndDevelopmentServicesForIONISFXILMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U002" decimals="-5">10100000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Amended in February 2017 with Bayer [Member]-IONIS-FXI-L [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20170228_ProductOrServiceAxis_IONISFXILMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U002" decimals="-5">64900000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in May 2015 with Bayer [Member]-Research and Development Services for IONIS-FXI [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20150531_ProductOrServiceAxis_ResearchAndDevelopmentServicesForIONISFXIMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U002" decimals="-5">4300000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in May 2015 with Bayer [Member]-IONIS-FXI Active Pharmaceutical Ingredient [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20150531_ProductOrServiceAxis_IONISFXIActivePharmaceuticalIngredientMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U002" decimals="-5">4500000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in December 2014 with Janssen Biotech, Inc. [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20141231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U002" decimals="-6">35000000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20130430_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6">30000000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in March 2010 with GSK [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20100331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-6">35000000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Delivery of AKCEA-APO(a)-L [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20170331_ProductOrServiceAxis_DeliveryOfAKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5">1500000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-Delivery of AKCEA-APOCIII-L [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20170331_ProductOrServiceAxis_DeliveryOfAKCEAAPOCIIILMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5">2800000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20170331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5">108400000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Research and Development Services for AKCEA-APO(a)-L [Member]-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20170331_ProductOrServiceAxis_ResearchAndDevelopmentServicesForAKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5">64000000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Revenue from Contract with Customer, Transaction Price-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-Research and Development Services for AKCEA-APOCIII-L [Member]-->
  <ions:RevenueFromContractWithCustomerTransactionPrice contextRef="c20170331_ProductOrServiceAxis_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5">40100000</ions:RevenueFromContractWithCustomerTransactionPrice>
  <!--Number of obligations fully satisfied-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with AstraZeneca [Member]-->
  <ions:NumberOfObligationsFullySatisified contextRef="c20140331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstraZenecaMember" unitRef="U005" decimals="INF">3</ions:NumberOfObligationsFullySatisified>
  <!--Number of drugs that can be licensed under option in collaboration agreements-Collaborative Arrangement and Licensing Agreement Entered Into in July 2015 with AstraZeneca [Member]-->
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  <!--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 December 2017 with Biogen [Member]-->
  <ions:UpfrontPaymentReceived contextRef="c20171201to20171231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U002" decimals="-6">25000000</ions:UpfrontPaymentReceived>
  <!--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 Entered Into in December 2012 with Biogen [Member]-->
  <ions:UpfrontPaymentReceived contextRef="c20121201to20121231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-6">30000000</ions:UpfrontPaymentReceived>
  <!--Upfront payment received-Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]-->
  <ions:UpfrontPaymentReceived contextRef="c20130901to20130930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6">100000000</ions:UpfrontPaymentReceived>
  <!--Upfront payment received-Collaborative Arrangement and Licensing Agreement Entered Into in April 2018 with Biogen [Member]-->
  <ions:UpfrontPaymentReceived contextRef="c20180401to20180630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U002" decimals="-6">375000000</ions:UpfrontPaymentReceived>
  <!--Upfront payment received-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with AstraZeneca [Member]-->
  <ions:UpfrontPaymentReceived contextRef="c20121201to20121231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstraZenecaMember" unitRef="U002" decimals="-6">31000000</ions:UpfrontPaymentReceived>
  <!--Upfront payment received-Collaborative Arrangement and Licensing Agreement Entered Into in July 2015 with AstraZeneca [Member]-->
  <ions:UpfrontPaymentReceived contextRef="c20150701to20150731_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstraZenecaMember" unitRef="U002" decimals="-6">65000000</ions:UpfrontPaymentReceived>
  <!--Upfront payment received-Collaborative Arrangement and Licensing Agreement Entered Into in May 2015 with Bayer [Member]-->
  <ions:UpfrontPaymentReceived contextRef="c20150401to20150630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U002" decimals="-6">100000000</ions:UpfrontPaymentReceived>
  <!--Upfront payment received-Collaborative Arrangement and Licensing Agreement Entered Into in December 2014 with Janssen Biotech, Inc. [Member]-->
  <ions:UpfrontPaymentReceived contextRef="c20141201to20141231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U002" decimals="-6">35000000</ions:UpfrontPaymentReceived>
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  <ions:UpfrontPaymentReceived contextRef="c20130401to20130430_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6">30000000</ions:UpfrontPaymentReceived>
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  <!--Upfront payment received-Collaborative Arrangement and Licensing Agreement Entered Into in March 2010 with GSK [Member]-->
  <ions:UpfrontPaymentReceived contextRef="c20100301to20100331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-6">35000000</ions:UpfrontPaymentReceived>
  <!--Upfront payment received-Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]-Akcea Therapeutics, Inc. [Member]-->
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  <ions:NextPotentialPayment contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U002" decimals="-5">7500000</ions:NextPotentialPayment>
  <!--Next potential payment-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]-->
  <ions:NextPotentialPayment contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-5">7500000</ions:NextPotentialPayment>
  <!--Next potential payment-Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]-->
  <ions:NextPotentialPayment contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6">10000000</ions:NextPotentialPayment>
  <!--Next potential payment-Collaborative Arrangement and Licensing Agreement Entered Into in December 2017 with Biogen [Member]-->
  <ions:NextPotentialPayment contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U002" decimals="-6">60000000</ions:NextPotentialPayment>
  <!--Next potential payment-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with AstraZeneca [Member]-->
  <ions:NextPotentialPayment contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstraZenecaMember" unitRef="U002" decimals="-5">25000000</ions:NextPotentialPayment>
  <!--Next potential payment-Collaborative Arrangement and Licensing Agreement Entered Into in July 2015 with AstraZeneca [Member]-->
  <ions:NextPotentialPayment contextRef="c20180930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstraZenecaMember" unitRef="U002" decimals="-6">10000000</ions:NextPotentialPayment>
  <!--Number of programs advanced-Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with AstraZeneca [Member]-Subsequent Event [Member]-->
  <ions:NumberOfProgramsAdvanced contextRef="c20181001to20181106_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstraZenecaMember" unitRef="U012" decimals="INF">2</ions:NumberOfProgramsAdvanced>
  <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>
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    <link:footnote xlink:label="Footnote-Item-3" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">At December 31, 2017, $3.5 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>
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    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-29_lbl" xlink:to="Footnote-Item-4" xlink:type="arc" />
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    <link:footnote xlink:label="Footnote-Item-5" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">Includes investments classified as cash equivalents on our condensed consolidated balance sheet.</link:footnote>
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    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-18_lbl" xlink:to="Footnote-Item-5" xlink:type="arc" />
    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-19_lbl" xlink:to="Footnote-Item-5" xlink:type="arc" />
    <link:footnoteArc order="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" xlink:from="Item-22_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">Included in cash and cash equivalents on our condensed consolidated balance sheet.</link:footnote>
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</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.LAB
<SEQUENCE>10
<FILENAME>ions-20180930_lab.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION LABEL LINKBASE
<TEXT>
<XBRL>
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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_AdjustmentsForNewAccountingPronouncementsAxis" xlink:label="AdjustmentsForNewAccountingPronouncementsAxis" xlink:title="AdjustmentsForNewAccountingPronouncementsAxis" />
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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_AllocatedShareBasedCompensationExpense" xlink:label="AllocatedShareBasedCompensationExpense" xlink:title="AllocatedShareBasedCompensationExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_AllocatedShareBasedCompensationExpense_lbl" xml:lang="en-US" id="us-gaap_AllocatedShareBasedCompensationExpense_lbl">Stock-based compensation expense</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AllocatedShareBasedCompensationExpense" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense_lbl1" xlink:title="label: AllocatedShareBasedCompensationExpense to us-gaap_AllocatedShareBasedCompensationExpense_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfDebtDiscountPremium_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AmortizationOfDebtDiscountPremium_lbl" xml:lang="en-US" id="us-gaap_AmortizationOfDebtDiscountPremium_lbl">Amortization of convertible senior notes discount</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfFinancingCosts_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AmortizationOfFinancingCosts_lbl1" xml:lang="en-US" id="us-gaap_AmortizationOfFinancingCosts_lbl1">Amortization of Debt Issuance Costs</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AmortizationOfLeasedAsset" xlink:label="AmortizationOfLeasedAsset" xlink:title="AmortizationOfLeasedAsset" />
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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_AssetImpairmentCharges" xlink:label="AssetImpairmentCharges" xlink:title="AssetImpairmentCharges" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsFairValueDisclosure_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_AssetsFairValueDisclosure_lbl" xml:lang="en-US" id="us-gaap_AssetsFairValueDisclosure_lbl">Total</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Assets" xlink:to="us-gaap_Assets_lbl" xlink:title="label: Assets to us-gaap_Assets_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Assets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Assets_lbl1" xml:lang="en-US" id="us-gaap_Assets_lbl1">Total assets as of current period</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskTypeDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskTypeDomain_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskTypeDomain_lbl">Concentration Risk Type [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskTypeDomain" xlink:to="us-gaap_ConcentrationRiskTypeDomain_lbl" xlink:title="label: ConcentrationRiskTypeDomain to us-gaap_ConcentrationRiskTypeDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:label="ConcentrationRiskByBenchmarkAxis" xlink:title="ConcentrationRiskByBenchmarkAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskByBenchmarkAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskByBenchmarkAxis_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskByBenchmarkAxis_lbl">Concentration Risk Benchmark [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskByBenchmarkAxis" xlink:to="us-gaap_ConcentrationRiskByBenchmarkAxis_lbl" xlink:title="label: ConcentrationRiskByBenchmarkAxis to us-gaap_ConcentrationRiskByBenchmarkAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ConcentrationRiskByTypeAxis" xlink:label="ConcentrationRiskByTypeAxis" xlink:title="ConcentrationRiskByTypeAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskByTypeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskByTypeAxis_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskByTypeAxis_lbl">Concentration Risk Type [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskByTypeAxis" xlink:to="us-gaap_ConcentrationRiskByTypeAxis_lbl" xlink:title="label: ConcentrationRiskByTypeAxis to us-gaap_ConcentrationRiskByTypeAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="ConcentrationRiskBenchmarkDomain" xlink:title="ConcentrationRiskBenchmarkDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskBenchmarkDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskBenchmarkDomain_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskBenchmarkDomain_lbl">Concentration Risk Benchmark [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskBenchmarkDomain" xlink:to="us-gaap_ConcentrationRiskBenchmarkDomain_lbl" xlink:title="label: ConcentrationRiskBenchmarkDomain to us-gaap_ConcentrationRiskBenchmarkDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ConcentrationRiskPercentage1" xlink:label="ConcentrationRiskPercentage1" xlink:title="ConcentrationRiskPercentage1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskPercentage1_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_ConcentrationRiskPercentage1_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskPercentage1_lbl">Concentration percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskPercentage1" xlink:to="us-gaap_ConcentrationRiskPercentage1_lbl" xlink:title="label: ConcentrationRiskPercentage1 to us-gaap_ConcentrationRiskPercentage1_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskPercentage1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskPercentage1_lbl1" xml:lang="en-US" id="us-gaap_ConcentrationRiskPercentage1_lbl1">Concentration percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskPercentage1" xlink:to="us-gaap_ConcentrationRiskPercentage1_lbl1" xlink:title="label: ConcentrationRiskPercentage1 to us-gaap_ConcentrationRiskPercentage1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ConsolidationPolicyTextBlock" xlink:label="ConsolidationPolicyTextBlock" xlink:title="ConsolidationPolicyTextBlock" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationPolicyTextBlock" xlink:to="us-gaap_ConsolidationPolicyTextBlock_lbl" xlink:title="label: ConsolidationPolicyTextBlock to us-gaap_ConsolidationPolicyTextBlock_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy" xlink:label="ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy" xlink:title="ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl" xml:lang="en-US" id="us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_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="ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy" xlink:to="us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl" xlink:title="label: ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy to us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl1" xml:lang="en-US" id="us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl1">Consolidation, Subsidiaries or Other Investments, Consolidated Entities, Policy [Policy 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_ContractWithCustomerLiabilityRevenueRecognized" xlink:label="ContractWithCustomerLiabilityRevenueRecognized" xlink:title="ContractWithCustomerLiabilityRevenueRecognized" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityRevenueRecognized" xlink:to="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" xlink:title="label: ContractWithCustomerLiabilityRevenueRecognized to us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1">Contract with Customer, Liability, Revenue Recognized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityRevenueRecognized" xlink:to="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" xlink:title="label: ContractWithCustomerLiabilityRevenueRecognized to us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:label="ContractWithCustomerLiabilityNoncurrent" xlink:title="ContractWithCustomerLiabilityNoncurrent" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1">Long-term portion of deferred revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityNoncurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" xlink:title="label: ContractWithCustomerLiabilityNoncurrent to us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl2" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl2">Contract with Customer, Liability, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityNoncurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl2" xlink:title="label: ContractWithCustomerLiabilityNoncurrent to us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ContractWithCustomerLiabilityAbstract" xlink:label="ContractWithCustomerLiabilityAbstract" xlink:title="ContractWithCustomerLiabilityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityAbstract_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityAbstract_lbl">Deferred Revenue [Abstract]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1">Contract with Customer, Liability [Abstract]</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_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" />
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    <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:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiability_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiability_lbl2" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiability_lbl2">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_lbl2" xlink:title="label: ContractWithCustomerLiability to us-gaap_ContractWithCustomerLiability_lbl2" />
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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_ContractWithCustomerLiabilityCurrent" xlink:label="ContractWithCustomerLiabilityCurrent" xlink:title="ContractWithCustomerLiabilityCurrent" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1">Current portion of deferred 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_lbl1" xlink:title="label: ContractWithCustomerLiabilityCurrent to us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityCurrent_lbl2" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityCurrent_lbl2">Contract with Customer, Liability, Current</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertiblePreferredStockTermsOfConversion_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertiblePreferredStockTermsOfConversion_lbl" xml:lang="en-US" id="us-gaap_ConvertiblePreferredStockTermsOfConversion_lbl">Conversion ratio</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertiblePreferredStockTermsOfConversion" xlink:to="us-gaap_ConvertiblePreferredStockTermsOfConversion_lbl" xlink:title="label: ConvertiblePreferredStockTermsOfConversion to us-gaap_ConvertiblePreferredStockTermsOfConversion_lbl" />
    <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_CreditFacilityAxis" xlink:label="CreditFacilityAxis" xlink:title="CreditFacilityAxis" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CreditFacilityAxis" xlink:to="us-gaap_CreditFacilityAxis_lbl" xlink:title="label: CreditFacilityAxis to us-gaap_CreditFacilityAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CreditFacilityDomain" xlink:label="CreditFacilityDomain" xlink:title="CreditFacilityDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CreditFacilityDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CreditFacilityDomain_lbl" xml:lang="en-US" id="us-gaap_CreditFacilityDomain_lbl">Credit Facility [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CreditFacilityDomain" xlink:to="us-gaap_CreditFacilityDomain_lbl" xlink:title="label: CreditFacilityDomain to us-gaap_CreditFacilityDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CreditConcentrationRiskMember" xlink:label="CreditConcentrationRiskMember" xlink:title="CreditConcentrationRiskMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CreditConcentrationRiskMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CreditConcentrationRiskMember_lbl" xml:lang="en-US" id="us-gaap_CreditConcentrationRiskMember_lbl">Credit Concentration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CreditConcentrationRiskMember" xlink:to="us-gaap_CreditConcentrationRiskMember_lbl" xlink:title="label: CreditConcentrationRiskMember to us-gaap_CreditConcentrationRiskMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="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 [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_DebtDisclosureAbstract" xlink:label="DebtDisclosureAbstract" xlink:title="DebtDisclosureAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtDisclosureAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtDisclosureAbstract_lbl" xml:lang="en-US" id="us-gaap_DebtDisclosureAbstract_lbl">Other Obligations [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtDisclosureAbstract" xlink:to="us-gaap_DebtDisclosureAbstract_lbl" xlink:title="label: DebtDisclosureAbstract to us-gaap_DebtDisclosureAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DebtInstrumentTerm" xlink:label="DebtInstrumentTerm" xlink:title="DebtInstrumentTerm" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentTerm_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentTerm_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentTerm_lbl">Term of agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentTerm" xlink:to="us-gaap_DebtInstrumentTerm_lbl" xlink:title="label: DebtInstrumentTerm to us-gaap_DebtInstrumentTerm_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DebtInstrumentDescriptionOfVariableRateBasis" xlink:label="DebtInstrumentDescriptionOfVariableRateBasis" xlink:title="DebtInstrumentDescriptionOfVariableRateBasis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentDescriptionOfVariableRateBasis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentDescriptionOfVariableRateBasis_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentDescriptionOfVariableRateBasis_lbl">Term of fixed rate elected</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentDescriptionOfVariableRateBasis" xlink:to="us-gaap_DebtInstrumentDescriptionOfVariableRateBasis_lbl" xlink:title="label: DebtInstrumentDescriptionOfVariableRateBasis to us-gaap_DebtInstrumentDescriptionOfVariableRateBasis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DebtAndCapitalLeasesDisclosuresTextBlock" xlink:label="DebtAndCapitalLeasesDisclosuresTextBlock" xlink:title="DebtAndCapitalLeasesDisclosuresTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtAndCapitalLeasesDisclosuresTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtAndCapitalLeasesDisclosuresTextBlock_lbl" xml:lang="en-US" id="us-gaap_DebtAndCapitalLeasesDisclosuresTextBlock_lbl">Other Obligations</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_DebtAndCapitalLeasesDisclosuresTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtAndCapitalLeasesDisclosuresTextBlock_lbl1" xml:lang="en-US" id="us-gaap_DebtAndCapitalLeasesDisclosuresTextBlock_lbl1">Debt and Capital Leases Disclosures [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtAndCapitalLeasesDisclosuresTextBlock" xlink:to="us-gaap_DebtAndCapitalLeasesDisclosuresTextBlock_lbl1" xlink:title="label: DebtAndCapitalLeasesDisclosuresTextBlock to us-gaap_DebtAndCapitalLeasesDisclosuresTextBlock_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtSecuritiesMember_lbl" xml:lang="en-US" id="us-gaap_DebtSecuritiesMember_lbl">Available-for-sale Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesMember" xlink:to="us-gaap_DebtSecuritiesMember_lbl" xlink:title="label: DebtSecuritiesMember to us-gaap_DebtSecuritiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesMember_lbl1">Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesMember" xlink:to="us-gaap_DebtSecuritiesMember_lbl1" xlink:title="label: DebtSecuritiesMember to us-gaap_DebtSecuritiesMember_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentNameDomain" xlink:to="us-gaap_DebtInstrumentNameDomain_lbl" xlink:title="label: DebtInstrumentNameDomain to us-gaap_DebtInstrumentNameDomain_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Depreciation" xlink:to="us-gaap_Depreciation_lbl" xlink:title="label: Depreciation to us-gaap_Depreciation_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Depreciation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Depreciation_lbl1" xml:lang="en-US" id="us-gaap_Depreciation_lbl1">Depreciation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Depreciation" xlink:to="us-gaap_Depreciation_lbl1" xlink:title="label: Depreciation to us-gaap_Depreciation_lbl1" />
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    <link: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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWriteDown_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryWriteDown_lbl1" xml:lang="en-US" id="us-gaap_InventoryWriteDown_lbl1">Inventory Write-down</link:label>
    <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: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_LicenseMember" xlink:label="LicenseMember" xlink:title="LicenseMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LicenseMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LicenseMember_lbl" xml:lang="en-US" id="us-gaap_LicenseMember_lbl">License Fees [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicenseMember" xlink:to="us-gaap_LicenseMember_lbl" xlink:title="label: LicenseMember to us-gaap_LicenseMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LicenseMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LicenseMember_lbl1" xml:lang="en-US" id="us-gaap_LicenseMember_lbl1">License [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicenseMember" xlink:to="us-gaap_LicenseMember_lbl1" xlink:title="label: LicenseMember to us-gaap_LicenseMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LineOfCreditFacilityTable" xlink:label="LineOfCreditFacilityTable" xlink:title="LineOfCreditFacilityTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LineOfCreditFacilityTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LineOfCreditFacilityTable_lbl" xml:lang="en-US" id="us-gaap_LineOfCreditFacilityTable_lbl">Line of Credit Facility [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LineOfCreditFacilityTable" xlink:to="us-gaap_LineOfCreditFacilityTable_lbl" xlink:title="label: LineOfCreditFacilityTable to us-gaap_LineOfCreditFacilityTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LineOfCreditFacilityLineItems" xlink:label="LineOfCreditFacilityLineItems" xlink:title="LineOfCreditFacilityLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LineOfCreditFacilityLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LineOfCreditFacilityLineItems_lbl" xml:lang="en-US" id="us-gaap_LineOfCreditFacilityLineItems_lbl">Line of Credit Facility [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LineOfCreditFacilityLineItems" xlink:to="us-gaap_LineOfCreditFacilityLineItems_lbl" xlink:title="label: LineOfCreditFacilityLineItems to us-gaap_LineOfCreditFacilityLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LineOfCreditFacilityAxis" xlink:label="LineOfCreditFacilityAxis" xlink:title="LineOfCreditFacilityAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LineOfCreditFacilityAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LineOfCreditFacilityAxis_lbl" xml:lang="en-US" id="us-gaap_LineOfCreditFacilityAxis_lbl">Lender Name [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LineOfCreditFacilityAxis" xlink:to="us-gaap_LineOfCreditFacilityAxis_lbl" xlink:title="label: LineOfCreditFacilityAxis to us-gaap_LineOfCreditFacilityAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LineOfCreditFacilityAbstract" xlink:label="LineOfCreditFacilityAbstract" xlink:title="LineOfCreditFacilityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LineOfCreditFacilityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LineOfCreditFacilityAbstract_lbl" xml:lang="en-US" id="us-gaap_LineOfCreditFacilityAbstract_lbl">Line of Credit Arrangement [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LineOfCreditFacilityAbstract" xlink:to="us-gaap_LineOfCreditFacilityAbstract_lbl" xlink:title="label: LineOfCreditFacilityAbstract to us-gaap_LineOfCreditFacilityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LineOfCreditFacilityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LineOfCreditFacilityAbstract_lbl1" xml:lang="en-US" id="us-gaap_LineOfCreditFacilityAbstract_lbl1">Line of Credit Facility [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LineOfCreditFacilityAbstract" xlink:to="us-gaap_LineOfCreditFacilityAbstract_lbl1" xlink:title="label: LineOfCreditFacilityAbstract to us-gaap_LineOfCreditFacilityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LineOfCreditFacilityUnusedCapacityCommitmentFeePercentage" xlink:label="LineOfCreditFacilityUnusedCapacityCommitmentFeePercentage" xlink:title="LineOfCreditFacilityUnusedCapacityCommitmentFeePercentage" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_LineOfCredit_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LineOfCredit_lbl" xml:lang="en-US" id="us-gaap_LineOfCredit_lbl">Outstanding borrowings</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LineOfCredit" xlink:to="us-gaap_LineOfCredit_lbl" xlink:title="label: LineOfCredit to us-gaap_LineOfCredit_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity" xlink:label="LineOfCreditFacilityMaximumBorrowingCapacity" xlink:title="LineOfCreditFacilityMaximumBorrowingCapacity" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_lbl" xml:lang="en-US" id="us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_lbl">Maximum borrowing capacity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LineOfCreditFacilityMaximumBorrowingCapacity" xlink:to="us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_lbl" xlink:title="label: LineOfCreditFacilityMaximumBorrowingCapacity to us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LineOfCreditFacilityLenderDomain" xlink:label="LineOfCreditFacilityLenderDomain" xlink:title="LineOfCreditFacilityLenderDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LineOfCreditFacilityLenderDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LineOfCreditFacilityLenderDomain_lbl" xml:lang="en-US" id="us-gaap_LineOfCreditFacilityLenderDomain_lbl">Line of Credit Facility, Lender [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LineOfCreditFacilityLenderDomain" xlink:to="us-gaap_LineOfCreditFacilityLenderDomain_lbl" xlink:title="label: LineOfCreditFacilityLenderDomain to us-gaap_LineOfCreditFacilityLenderDomain_lbl" />
    <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>
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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_ManufacturingFacilityMember" xlink:label="ManufacturingFacilityMember" xlink:title="ManufacturingFacilityMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ManufacturingFacilityMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ManufacturingFacilityMember_lbl" xml:lang="en-US" id="us-gaap_ManufacturingFacilityMember_lbl">Manufacturing Facility [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ManufacturingFacilityMember" xlink:to="us-gaap_ManufacturingFacilityMember_lbl" xlink:title="label: ManufacturingFacilityMember to us-gaap_ManufacturingFacilityMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ManufacturingFacilityMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ManufacturingFacilityMember_lbl1" xml:lang="en-US" id="us-gaap_ManufacturingFacilityMember_lbl1">Manufacturing Facility [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ManufacturingFacilityMember" xlink:to="us-gaap_ManufacturingFacilityMember_lbl1" xlink:title="label: ManufacturingFacilityMember to us-gaap_ManufacturingFacilityMember_lbl1" />
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    <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" />
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    <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" />
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    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterestLineItems" xlink:to="us-gaap_MinorityInterestLineItems_lbl" xlink:title="label: MinorityInterestLineItems to us-gaap_MinorityInterestLineItems_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_VariableRateDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_VariableRateDomain_lbl" xml:lang="en-US" id="us-gaap_VariableRateDomain_lbl">Variable Rate [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="VariableRateDomain" xlink:to="us-gaap_VariableRateDomain_lbl" xlink:title="label: VariableRateDomain to us-gaap_VariableRateDomain_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl">Shares used in computing basic net income (loss) per share (in shares)</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_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:label="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:title="WeightedAverageNumberOfDilutedSharesOutstanding" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidatedEntitiesDomain" xlink:to="srt_ConsolidatedEntitiesDomain_lbl" xlink:title="label: ConsolidatedEntitiesDomain to srt_ConsolidatedEntitiesDomain_lbl" />
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    <link:label xlink:type="resource" xlink:label="srt_ConsolidationItemsAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ConsolidationItemsAxis_lbl" xml:lang="en-US" id="srt_ConsolidationItemsAxis_lbl">Consolidation Items [Axis]</link:label>
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    <link:label xlink:type="resource" xlink:label="srt_ConsolidationItemsDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ConsolidationItemsDomain_lbl" xml:lang="en-US" id="srt_ConsolidationItemsDomain_lbl">Consolidation Items [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationItemsDomain" xlink:to="srt_ConsolidationItemsDomain_lbl" xlink:title="label: ConsolidationItemsDomain to srt_ConsolidationItemsDomain_lbl" />
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    <link:label xlink:type="resource" xlink:label="srt_MinimumMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_MinimumMember_lbl" xml:lang="en-US" id="srt_MinimumMember_lbl">Minimum [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="srt_OwnershipDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_OwnershipDomain_lbl" xml:lang="en-US" id="srt_OwnershipDomain_lbl">Ownership [Domain]</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_OwnershipAxis" xlink:label="OwnershipAxis" xlink:title="OwnershipAxis" />
    <link:label xlink:type="resource" xlink:label="srt_OwnershipAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_OwnershipAxis_lbl" xml:lang="en-US" id="srt_OwnershipAxis_lbl">Ownership [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OwnershipAxis" xlink:to="srt_OwnershipAxis_lbl" xlink:title="label: OwnershipAxis to srt_OwnershipAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductsAndServicesDomain" xlink:to="srt_ProductsAndServicesDomain_lbl" xlink:title="label: ProductsAndServicesDomain to srt_ProductsAndServicesDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:label xlink:type="resource" xlink:label="srt_ProductOrServiceAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ProductOrServiceAxis_lbl" xml:lang="en-US" id="srt_ProductOrServiceAxis_lbl">Products and Services [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductOrServiceAxis" xlink:to="srt_ProductOrServiceAxis_lbl" xlink:title="label: ProductOrServiceAxis to srt_ProductOrServiceAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeMember" xlink:label="RangeMember" xlink:title="RangeMember" />
    <link:label xlink:type="resource" xlink:label="srt_RangeMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_RangeMember_lbl" xml:lang="en-US" id="srt_RangeMember_lbl">Range [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RangeMember" xlink:to="srt_RangeMember_lbl" xlink:title="label: RangeMember to srt_RangeMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd#srt_RangeAxis" xlink:label="RangeAxis" xlink:title="RangeAxis" />
    <link:label xlink:type="resource" xlink:label="srt_RangeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_RangeAxis_lbl" xml:lang="en-US" id="srt_RangeAxis_lbl">Range [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RangeAxis" xlink:to="srt_RangeAxis_lbl" xlink:title="label: RangeAxis to srt_RangeAxis_lbl" />
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    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_AntisenseMoleculeMember" xlink:label="AntisenseMoleculeMember" xlink:title="AntisenseMoleculeMember" />
    <link:label xlink:type="resource" xlink:label="ions_AntisenseMoleculeMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AntisenseMoleculeMember_lbl" xml:lang="en-US" id="ions_AntisenseMoleculeMember_lbl">Each antisense molecule that is chosen for drug discovery and development to advance the treatment of neurological diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AntisenseMoleculeMember" xlink:to="ions_AntisenseMoleculeMember_lbl" xlink:title="label: AntisenseMoleculeMember to ions_AntisenseMoleculeMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AntisenseMoleculeMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AntisenseMoleculeMember_lbl1" xml:lang="en-US" id="ions_AntisenseMoleculeMember_lbl1">Antisense Molecule [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AntisenseMoleculeMember" xlink:to="ions_AntisenseMoleculeMember_lbl1" xlink:title="label: AntisenseMoleculeMember to ions_AntisenseMoleculeMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones" xlink:label="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones" xlink:title="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl">The maximum amount of payments receivable per drug or program for development milestone payments under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl1">Maximum amount of payments receivable per drug or program for development milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl2">Maximum amount of payments receivable per program for development milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl" xml:lang="en-US" id="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl">Cumulative 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.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" xlink:to="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl" xlink:title="label: CumulativeRevenueFromContractWithCustomerExcludingAssessedTax to ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xml:lang="en-US" id="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl1">Cumulative Revenue from Contract with Customer, Excluding Assessed Tax</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" xlink:to="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xlink:title="label: CumulativeRevenueFromContractWithCustomerExcludingAssessedTax to ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl2" xml:lang="en-US" id="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl2">Cumulative revenue earned</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" xlink:to="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl2" xlink:title="label: CumulativeRevenueFromContractWithCustomerExcludingAssessedTax to ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_NumberOfDrugsCurrentlyBeingAdvanced" xlink:label="NumberOfDrugsCurrentlyBeingAdvanced" xlink:title="NumberOfDrugsCurrentlyBeingAdvanced" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl" xml:lang="en-US" id="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl">The number of drugs currently being advanced under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfDrugsCurrentlyBeingAdvanced" xlink:to="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl" xlink:title="label: NumberOfDrugsCurrentlyBeingAdvanced to ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl1" xml:lang="en-US" id="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl1">Number of drugs currently being advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfDrugsCurrentlyBeingAdvanced" xlink:to="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl1" xlink:title="label: NumberOfDrugsCurrentlyBeingAdvanced to ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl2" xml:lang="en-US" id="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl2">Number of drugs currently being advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfDrugsCurrentlyBeingAdvanced" xlink:to="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl2" xlink:title="label: NumberOfDrugsCurrentlyBeingAdvanced to ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_NumberOfTargets" xlink:label="NumberOfTargets" xlink:title="NumberOfTargets" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTargets_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfTargets_lbl" xml:lang="en-US" id="ions_NumberOfTargets_lbl">The number of targets for the research and development of drugs under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTargets" xlink:to="ions_NumberOfTargets_lbl" xlink:title="label: NumberOfTargets to ions_NumberOfTargets_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTargets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfTargets_lbl1" xml:lang="en-US" id="ions_NumberOfTargets_lbl1">Number of targets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTargets" xlink:to="ions_NumberOfTargets_lbl1" xlink:title="label: NumberOfTargets to ions_NumberOfTargets_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTargets_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfTargets_lbl2" xml:lang="en-US" id="ions_NumberOfTargets_lbl2">Number of targets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTargets" xlink:to="ions_NumberOfTargets_lbl2" xlink:title="label: NumberOfTargets to ions_NumberOfTargets_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" xlink:label="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" xlink:title="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl">The maximum amount of payments receivable per drug or program for license fees and/or substantive milestone payments under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl1">Maximum amount of payments receivable per drug or program for license fees and substantive milestone payments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl2">Maximum amount of payments receivable per program for license fee and substantive milestone payments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Biogen Inc. in September 2013. This agreement is a long-term strategic relationship focused on applying antisense technology to advance the treatment of neurodegenerative diseases (Strategic Neurology).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl2">2013 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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-20180930.xsd#ions_OtherModalitiesMember" xlink:label="OtherModalitiesMember" xlink:title="OtherModalitiesMember" />
    <link:label xlink:type="resource" xlink:label="ions_OtherModalitiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OtherModalitiesMember_lbl" xml:lang="en-US" id="ions_OtherModalitiesMember_lbl">Other modalities, such as small molecules or monoclonal antibodies, chosen for drug discovery and development to advance the treatment of neurological diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherModalitiesMember" xlink:to="ions_OtherModalitiesMember_lbl" xlink:title="label: OtherModalitiesMember to ions_OtherModalitiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OtherModalitiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OtherModalitiesMember_lbl1" xml:lang="en-US" id="ions_OtherModalitiesMember_lbl1">Other Modalities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherModalitiesMember" xlink:to="ions_OtherModalitiesMember_lbl1" xlink:title="label: OtherModalitiesMember to ions_OtherModalitiesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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/terseLabel" xlink:title="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2" xml:lang="en-US" id="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2">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_lbl2" xlink:title="label: UpfrontPaymentReceivedIncludingPurchaseOfStock to ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_MaximumAmountOfPaymentsReceivableForSalesMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForSalesMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForSalesMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl">The maximum amount of payments receivable for sales milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForSalesMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForSalesMilestones to ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl1">Maximum amount of payments receivable for sales milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForSalesMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForSalesMilestones to ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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-20180930.xsd#ions_PercentageCashPremiumPaidOnSharesPurchased" xlink:label="PercentageCashPremiumPaidOnSharesPurchased" xlink:title="PercentageCashPremiumPaidOnSharesPurchased" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl" xml:lang="en-US" id="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl">The percentage cash premium paid per share of the Company's common stock under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageCashPremiumPaidOnSharesPurchased" xlink:to="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl" xlink:title="label: PercentageCashPremiumPaidOnSharesPurchased to ions_PercentageCashPremiumPaidOnSharesPurchased_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl1" xml:lang="en-US" id="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl1">Percentage cash premium paid on shares purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageCashPremiumPaidOnSharesPurchased" xlink:to="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl1" xlink:title="label: PercentageCashPremiumPaidOnSharesPurchased to ions_PercentageCashPremiumPaidOnSharesPurchased_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl2" xml:lang="en-US" id="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl2">Percentage cash premium paid on shares purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageCashPremiumPaidOnSharesPurchased" xlink:to="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl2" xlink:title="label: PercentageCashPremiumPaidOnSharesPurchased to ions_PercentageCashPremiumPaidOnSharesPurchased_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PremiumPaidOnSharesPurchased" xlink:label="PremiumPaidOnSharesPurchased" xlink:title="PremiumPaidOnSharesPurchased" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumPaidOnSharesPurchased_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PremiumPaidOnSharesPurchased_lbl" xml:lang="en-US" id="ions_PremiumPaidOnSharesPurchased_lbl">The cash premium paid on the purchase of the Company's common stock under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumPaidOnSharesPurchased" xlink:to="ions_PremiumPaidOnSharesPurchased_lbl" xlink:title="label: PremiumPaidOnSharesPurchased to ions_PremiumPaidOnSharesPurchased_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumPaidOnSharesPurchased_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PremiumPaidOnSharesPurchased_lbl1" xml:lang="en-US" id="ions_PremiumPaidOnSharesPurchased_lbl1">Premium paid on shares purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumPaidOnSharesPurchased" xlink:to="ions_PremiumPaidOnSharesPurchased_lbl1" xlink:title="label: PremiumPaidOnSharesPurchased to ions_PremiumPaidOnSharesPurchased_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumPaidOnSharesPurchased_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PremiumPaidOnSharesPurchased_lbl2" xml:lang="en-US" id="ions_PremiumPaidOnSharesPurchased_lbl2">Premium paid on shares purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumPaidOnSharesPurchased" xlink:to="ions_PremiumPaidOnSharesPurchased_lbl2" xlink:title="label: PremiumPaidOnSharesPurchased to ions_PremiumPaidOnSharesPurchased_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_TermOfCollaborationAgreement" xlink:label="TermOfCollaborationAgreement" xlink:title="TermOfCollaborationAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_TermOfCollaborationAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_TermOfCollaborationAgreement_lbl" xml:lang="en-US" id="ions_TermOfCollaborationAgreement_lbl">Term of the collaboration agreement, 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="TermOfCollaborationAgreement" xlink:to="ions_TermOfCollaborationAgreement_lbl" xlink:title="label: TermOfCollaborationAgreement to ions_TermOfCollaborationAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_TermOfCollaborationAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_TermOfCollaborationAgreement_lbl1" xml:lang="en-US" id="ions_TermOfCollaborationAgreement_lbl1">Term of collaboration agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TermOfCollaborationAgreement" xlink:to="ions_TermOfCollaborationAgreement_lbl1" xlink:title="label: TermOfCollaborationAgreement to ions_TermOfCollaborationAgreement_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_TermOfCollaborationAgreement_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_TermOfCollaborationAgreement_lbl2" xml:lang="en-US" id="ions_TermOfCollaborationAgreement_lbl2">Term of collaboration agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TermOfCollaborationAgreement" xlink:to="ions_TermOfCollaborationAgreement_lbl2" xlink:title="label: TermOfCollaborationAgreement to ions_TermOfCollaborationAgreement_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Janssen Biotech, Inc. in December 2014 to discover and develop antisense drugs that can be locally administered, including oral delivery, to treat autoimmune disorders of the gastrointestinal tract.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in December 2014 with Janssen Biotech, Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl2">Janssen Biotech, Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized" xlink:label="NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized" xlink:title="NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl" xml:lang="en-US" id="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl">The number of programs under which drugs are to be developed and commercialized under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized" xlink:to="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl" xlink:title="label: NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized to ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl1" xml:lang="en-US" id="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl1">Number of programs under which drugs are to be developed and commercialized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized" xlink:to="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl1" xlink:title="label: NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized to ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl2" xml:lang="en-US" id="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl2">Number of programs under which drugs are to be developed and commercialized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized" xlink:to="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl2" xlink:title="label: NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized to ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_IONISJBI225Member" xlink:label="IONISJBI225Member" xlink:title="IONISJBI225Member" />
    <link:label xlink:type="resource" xlink:label="ions_IONISJBI225Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IONISJBI225Member_lbl1" xml:lang="en-US" id="ions_IONISJBI225Member_lbl1">IONIS-JBI2-2.5 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISJBI225Member" xlink:to="ions_IONISJBI225Member_lbl1" xlink:title="label: IONISJBI225Member to ions_IONISJBI225Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IONISJBI225Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IONISJBI225Member_lbl2" xml:lang="en-US" id="ions_IONISJBI225Member_lbl2">IONIS-JBI2-2.5 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISJBI225Member" xlink:to="ions_IONISJBI225Member_lbl2" xlink:title="label: IONISJBI225Member to ions_IONISJBI225Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_IONISJBI125Member" xlink:label="IONISJBI125Member" xlink:title="IONISJBI125Member" />
    <link:label xlink:type="resource" xlink:label="ions_IONISJBI125Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IONISJBI125Member_lbl1" xml:lang="en-US" id="ions_IONISJBI125Member_lbl1">IONIS-JBI1-2.5 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISJBI125Member" xlink:to="ions_IONISJBI125Member_lbl1" xlink:title="label: IONISJBI125Member to ions_IONISJBI125Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IONISJBI125Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IONISJBI125Member_lbl2" xml:lang="en-US" id="ions_IONISJBI125Member_lbl2">IONIS-JBI1-2.5 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISJBI125Member" xlink:to="ions_IONISJBI125Member_lbl2" xlink:title="label: IONISJBI125Member to ions_IONISJBI125Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:label="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:title="RoyaltyPercentageReceivedOnNetSalesOfDrug" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl">Royalty percentage received on the net sales of a drug by a collaboration partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfDrug to ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl1">Royalty percentage received on net sales of drug</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfDrug to ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl2" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfDrug to ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in October 2018 to develop IONIS-FB-LRx for the treatment of complement-mediated diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl1" />
    <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 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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-20180930.xsd#ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped" xlink:label="MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped" xlink:title="MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl">The maximum amount of payments receivable for each additional drug developed under the collaboration agreement.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl1">Maximum amount of payment receivable for each additional drug developed</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped" xlink:to="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl1" xlink:title="label: MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped to ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl2">Maximum amount of payment receivable for each additional drug developed</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped" xlink:to="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl2" xlink:title="label: MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped to ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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-20180930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in April 2013 to develop treatments for Huntington's disease, or HD, based on the Company's antisense technology.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]</link:label>
    <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" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl2">Huntington's Disease [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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/terseLabel" xlink:title="ions_MilestonePaymentsReceived_lbl2" xml:lang="en-US" id="ions_MilestonePaymentsReceived_lbl2">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_lbl2" xlink:title="label: MilestonePaymentsReceived to ions_MilestonePaymentsReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xlink:label="PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xlink:title="PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl" xml:lang="en-US" id="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl">Period of time to make only payments of interest on the mortgage loan, 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="PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xlink:to="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl" xlink:title="label: PeriodToMakeInterestOnlyPaymentsOnMortgageLoan to ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl1" xml:lang="en-US" id="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl1">Period to make interest only payments on mortgage loan</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xlink:to="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl1" xlink:title="label: PeriodToMakeInterestOnlyPaymentsOnMortgageLoan to ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl2" xml:lang="en-US" id="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl2">Period to make interest only payments on mortgage loan</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xlink:to="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl2" xlink:title="label: PeriodToMakeInterestOnlyPaymentsOnMortgageLoan to ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PrimaryResearchAndDevelopmentFacilityMember" xlink:label="PrimaryResearchAndDevelopmentFacilityMember" xlink:title="PrimaryResearchAndDevelopmentFacilityMember" />
    <link:label xlink:type="resource" xlink:label="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl" xml:lang="en-US" id="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl">Facility constructed for the entity's primary research and development activities under a lease agreement with an affiliate of BioMed Realty, L.P.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PrimaryResearchAndDevelopmentFacilityMember" xlink:to="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl" xlink:title="label: PrimaryResearchAndDevelopmentFacilityMember to ions_PrimaryResearchAndDevelopmentFacilityMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl1" xml:lang="en-US" id="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl1">Primary Research and Development Facility [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PrimaryResearchAndDevelopmentFacilityMember" xlink:to="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl1" xlink:title="label: PrimaryResearchAndDevelopmentFacilityMember to ions_PrimaryResearchAndDevelopmentFacilityMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl2" xml:lang="en-US" id="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl2">Primary R&amp;D Facility [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PrimaryResearchAndDevelopmentFacilityMember" xlink:to="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl2" xlink:title="label: PrimaryResearchAndDevelopmentFacilityMember to ions_PrimaryResearchAndDevelopmentFacilityMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_AdditionalAmountOfCommonStockRequiredToBePurchased" xlink:label="AdditionalAmountOfCommonStockRequiredToBePurchased" xlink:title="AdditionalAmountOfCommonStockRequiredToBePurchased" />
    <link:label xlink:type="resource" xlink:label="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl" xml:lang="en-US" id="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl">The additional amount of common stock the collaboration partner is required to purchase under a Stock Purchase Agreement (SPA) in conjunction with the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AdditionalAmountOfCommonStockRequiredToBePurchased" xlink:to="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl" xlink:title="label: AdditionalAmountOfCommonStockRequiredToBePurchased to ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl1" xml:lang="en-US" id="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl1">Additional amount of common stock required to be purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AdditionalAmountOfCommonStockRequiredToBePurchased" xlink:to="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl1" xlink:title="label: AdditionalAmountOfCommonStockRequiredToBePurchased to ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl2" xml:lang="en-US" id="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl2">Additional amount of common stock required to be purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AdditionalAmountOfCommonStockRequiredToBePurchased" xlink:to="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl2" xlink:title="label: AdditionalAmountOfCommonStockRequiredToBePurchased to ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_FutureStockPurchaseAbstract" xlink:label="FutureStockPurchaseAbstract" xlink:title="FutureStockPurchaseAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_FutureStockPurchaseAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_FutureStockPurchaseAbstract_lbl1" xml:lang="en-US" id="ions_FutureStockPurchaseAbstract_lbl1">Future Stock Purchase [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FutureStockPurchaseAbstract" xlink:to="ions_FutureStockPurchaseAbstract_lbl1" xlink:title="label: FutureStockPurchaseAbstract to ions_FutureStockPurchaseAbstract_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_FutureStockPurchaseAbstract_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_FutureStockPurchaseAbstract_lbl2" xml:lang="en-US" id="ions_FutureStockPurchaseAbstract_lbl2">Novartis Future Stock Purchase [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FutureStockPurchaseAbstract" xlink:to="ions_FutureStockPurchaseAbstract_lbl2" xlink:title="label: FutureStockPurchaseAbstract to ions_FutureStockPurchaseAbstract_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PotentialFuturePremiumMember" xlink:label="PotentialFuturePremiumMember" xlink:title="PotentialFuturePremiumMember" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialFuturePremiumMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PotentialFuturePremiumMember_lbl" xml:lang="en-US" id="ions_PotentialFuturePremiumMember_lbl">The potential future premium that will be received if Novartis purchases the Company's common stock at a percentage premium over the trading price of the common stock at the time of purchase under the terms of a Stock Purchase Agreement (SPA).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialFuturePremiumMember" xlink:to="ions_PotentialFuturePremiumMember_lbl" xlink:title="label: PotentialFuturePremiumMember to ions_PotentialFuturePremiumMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialFuturePremiumMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PotentialFuturePremiumMember_lbl1" xml:lang="en-US" id="ions_PotentialFuturePremiumMember_lbl1">Potential Future Premium [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialFuturePremiumMember" xlink:to="ions_PotentialFuturePremiumMember_lbl1" xlink:title="label: PotentialFuturePremiumMember to ions_PotentialFuturePremiumMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialFuturePremiumMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PotentialFuturePremiumMember_lbl2" xml:lang="en-US" id="ions_PotentialFuturePremiumMember_lbl2">Potential Future Premium [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialFuturePremiumMember" xlink:to="ions_PotentialFuturePremiumMember_lbl2" xlink:title="label: PotentialFuturePremiumMember to ions_PotentialFuturePremiumMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PotentialFuturePremium" xlink:label="PotentialFuturePremium" xlink:title="PotentialFuturePremium" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialFuturePremium_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PotentialFuturePremium_lbl" xml:lang="en-US" id="ions_PotentialFuturePremium_lbl">The fair value of the potential future premium the Company will receive if Novartis purchases its common stock under a Stock Purchase Agreement (SPA) entered into in January 2017.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialFuturePremium" xlink:to="ions_PotentialFuturePremium_lbl" xlink:title="label: PotentialFuturePremium to ions_PotentialFuturePremium_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialFuturePremium_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PotentialFuturePremium_lbl1" xml:lang="en-US" id="ions_PotentialFuturePremium_lbl1">Potential future premium</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialFuturePremium" xlink:to="ions_PotentialFuturePremium_lbl1" xlink:title="label: PotentialFuturePremium to ions_PotentialFuturePremium_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialFuturePremium_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PotentialFuturePremium_lbl2" xml:lang="en-US" id="ions_PotentialFuturePremium_lbl2">Fair value of potential future premium</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialFuturePremium" xlink:to="ions_PotentialFuturePremium_lbl2" xlink:title="label: PotentialFuturePremium to ions_PotentialFuturePremium_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_DeliveryOfAKCEAAPOCIIILMember" xlink:label="DeliveryOfAKCEAAPOCIIILMember" xlink:title="DeliveryOfAKCEAAPOCIIILMember" />
    <link:label xlink:type="resource" xlink:label="ions_DeliveryOfAKCEAAPOCIIILMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DeliveryOfAKCEAAPOCIIILMember_lbl" xml:lang="en-US" id="ions_DeliveryOfAKCEAAPOCIIILMember_lbl">Delivery of AKCEA-APOCIII-L, an antisense therapy with the potential to significantly reduce cardiovascular risk in patients suffering from high levels of the lipoprotein ApoCIII.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeliveryOfAKCEAAPOCIIILMember" xlink:to="ions_DeliveryOfAKCEAAPOCIIILMember_lbl" xlink:title="label: DeliveryOfAKCEAAPOCIIILMember to ions_DeliveryOfAKCEAAPOCIIILMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DeliveryOfAKCEAAPOCIIILMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DeliveryOfAKCEAAPOCIIILMember_lbl1" xml:lang="en-US" id="ions_DeliveryOfAKCEAAPOCIIILMember_lbl1">Delivery of AKCEA-APOCIII-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeliveryOfAKCEAAPOCIIILMember" xlink:to="ions_DeliveryOfAKCEAAPOCIIILMember_lbl1" xlink:title="label: DeliveryOfAKCEAAPOCIIILMember to ions_DeliveryOfAKCEAAPOCIIILMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DeliveryOfAKCEAAPOCIIILMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DeliveryOfAKCEAAPOCIIILMember_lbl2" xml:lang="en-US" id="ions_DeliveryOfAKCEAAPOCIIILMember_lbl2">Delivery of AKCEA-APOCIII-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeliveryOfAKCEAAPOCIIILMember" xlink:to="ions_DeliveryOfAKCEAAPOCIIILMember_lbl2" xlink:title="label: DeliveryOfAKCEAAPOCIIILMember to ions_DeliveryOfAKCEAAPOCIIILMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_DeliveryOfAKCEAAPOALMember" xlink:label="DeliveryOfAKCEAAPOALMember" xlink:title="DeliveryOfAKCEAAPOALMember" />
    <link:label xlink:type="resource" xlink:label="ions_DeliveryOfAKCEAAPOALMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DeliveryOfAKCEAAPOALMember_lbl" xml:lang="en-US" id="ions_DeliveryOfAKCEAAPOALMember_lbl">Delivery of AKCEA-APO(a)-L, 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="DeliveryOfAKCEAAPOALMember" xlink:to="ions_DeliveryOfAKCEAAPOALMember_lbl" xlink:title="label: DeliveryOfAKCEAAPOALMember to ions_DeliveryOfAKCEAAPOALMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DeliveryOfAKCEAAPOALMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DeliveryOfAKCEAAPOALMember_lbl1" xml:lang="en-US" id="ions_DeliveryOfAKCEAAPOALMember_lbl1">Delivery of AKCEA-APO(a)-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeliveryOfAKCEAAPOALMember" xlink:to="ions_DeliveryOfAKCEAAPOALMember_lbl1" xlink:title="label: DeliveryOfAKCEAAPOALMember to ions_DeliveryOfAKCEAAPOALMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DeliveryOfAKCEAAPOALMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DeliveryOfAKCEAAPOALMember_lbl2" xml:lang="en-US" id="ions_DeliveryOfAKCEAAPOALMember_lbl2">Delivery of AKCEA-APO(a)-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeliveryOfAKCEAAPOALMember" xlink:to="ions_DeliveryOfAKCEAAPOALMember_lbl2" xlink:title="label: DeliveryOfAKCEAAPOALMember to ions_DeliveryOfAKCEAAPOALMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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-20180930.xsd#ions_AKCEAAPOCIIILMember" xlink:label="AKCEAAPOCIIILMember" xlink:title="AKCEAAPOCIIILMember" />
    <link:label xlink:type="resource" xlink:label="ions_AKCEAAPOCIIILMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AKCEAAPOCIIILMember_lbl" xml:lang="en-US" id="ions_AKCEAAPOCIIILMember_lbl">An antisense therapy with the potential to significantly reduce cardiovascular risk in patients suffering from high levels of the lipoprotein ApoCIII.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AKCEAAPOCIIILMember" xlink:to="ions_AKCEAAPOCIIILMember_lbl" xlink:title="label: AKCEAAPOCIIILMember to ions_AKCEAAPOCIIILMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AKCEAAPOCIIILMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AKCEAAPOCIIILMember_lbl1" xml:lang="en-US" id="ions_AKCEAAPOCIIILMember_lbl1">AKCEA-APOCIII-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AKCEAAPOCIIILMember" xlink:to="ions_AKCEAAPOCIIILMember_lbl1" xlink:title="label: AKCEAAPOCIIILMember to ions_AKCEAAPOCIIILMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AKCEAAPOCIIILMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AKCEAAPOCIIILMember_lbl2" xml:lang="en-US" id="ions_AKCEAAPOCIIILMember_lbl2">AKCEA-APOCIII-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AKCEAAPOCIIILMember" xlink:to="ions_AKCEAAPOCIIILMember_lbl2" xlink:title="label: AKCEAAPOCIIILMember to ions_AKCEAAPOCIIILMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PortionOfUpfrontPaymentRetained" xlink:label="PortionOfUpfrontPaymentRetained" xlink:title="PortionOfUpfrontPaymentRetained" />
    <link:label xlink:type="resource" xlink:label="ions_PortionOfUpfrontPaymentRetained_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PortionOfUpfrontPaymentRetained_lbl" xml:lang="en-US" id="ions_PortionOfUpfrontPaymentRetained_lbl">The amount of the upfront payment received during the period under the collaboration agreement that was retained by the entity.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PortionOfUpfrontPaymentRetained" xlink:to="ions_PortionOfUpfrontPaymentRetained_lbl" xlink:title="label: PortionOfUpfrontPaymentRetained to ions_PortionOfUpfrontPaymentRetained_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PortionOfUpfrontPaymentRetained_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PortionOfUpfrontPaymentRetained_lbl1" xml:lang="en-US" id="ions_PortionOfUpfrontPaymentRetained_lbl1">Portion of upfront payment retained</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PortionOfUpfrontPaymentRetained" xlink:to="ions_PortionOfUpfrontPaymentRetained_lbl1" xlink:title="label: PortionOfUpfrontPaymentRetained to ions_PortionOfUpfrontPaymentRetained_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PortionOfUpfrontPaymentRetained_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PortionOfUpfrontPaymentRetained_lbl2" xml:lang="en-US" id="ions_PortionOfUpfrontPaymentRetained_lbl2">Portion of upfront payment retained</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PortionOfUpfrontPaymentRetained" xlink:to="ions_PortionOfUpfrontPaymentRetained_lbl2" xlink:title="label: PortionOfUpfrontPaymentRetained to ions_PortionOfUpfrontPaymentRetained_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PortionOfUpfrontPaymentPaidAsASublicenseFee" xlink:label="PortionOfUpfrontPaymentPaidAsASublicenseFee" xlink:title="PortionOfUpfrontPaymentPaidAsASublicenseFee" />
    <link:label xlink:type="resource" xlink:label="ions_PortionOfUpfrontPaymentPaidAsASublicenseFee_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PortionOfUpfrontPaymentPaidAsASublicenseFee_lbl" xml:lang="en-US" id="ions_PortionOfUpfrontPaymentPaidAsASublicenseFee_lbl">The amount of the upfront payment received during the period under the collaboration agreement that was paid as a sublicense fee.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PortionOfUpfrontPaymentPaidAsASublicenseFee" xlink:to="ions_PortionOfUpfrontPaymentPaidAsASublicenseFee_lbl" xlink:title="label: PortionOfUpfrontPaymentPaidAsASublicenseFee to ions_PortionOfUpfrontPaymentPaidAsASublicenseFee_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PortionOfUpfrontPaymentPaidAsASublicenseFee_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PortionOfUpfrontPaymentPaidAsASublicenseFee_lbl1" xml:lang="en-US" id="ions_PortionOfUpfrontPaymentPaidAsASublicenseFee_lbl1">Portion of upfront payment paid as a sublicense fee</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PortionOfUpfrontPaymentPaidAsASublicenseFee" xlink:to="ions_PortionOfUpfrontPaymentPaidAsASublicenseFee_lbl1" xlink:title="label: PortionOfUpfrontPaymentPaidAsASublicenseFee to ions_PortionOfUpfrontPaymentPaidAsASublicenseFee_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PortionOfUpfrontPaymentPaidAsASublicenseFee_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PortionOfUpfrontPaymentPaidAsASublicenseFee_lbl2" xml:lang="en-US" id="ions_PortionOfUpfrontPaymentPaidAsASublicenseFee_lbl2">Portion of upfront payment paid as a sublicense fee</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PortionOfUpfrontPaymentPaidAsASublicenseFee" xlink:to="ions_PortionOfUpfrontPaymentPaidAsASublicenseFee_lbl2" xlink:title="label: PortionOfUpfrontPaymentPaidAsASublicenseFee to ions_PortionOfUpfrontPaymentPaidAsASublicenseFee_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_MaximumAmountOfPaymentsReceivableForMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl">The maximum amount of payments receivable for milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForMilestones to ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl1">Maximum amount of payments receivable for milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForMilestones to ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl2">Maximum amount of payments receivable for milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableForMilestones to ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_RoyaltyPercentageReceivedOnSalesOfDrug" xlink:label="RoyaltyPercentageReceivedOnSalesOfDrug" xlink:title="RoyaltyPercentageReceivedOnSalesOfDrug" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl">Royalty percentage received on the sales of a drug by a collaboration partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnSalesOfDrug" xlink:to="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl" xlink:title="label: RoyaltyPercentageReceivedOnSalesOfDrug to ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl1">Royalty percentage received on sales of drug</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnSalesOfDrug" xlink:to="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnSalesOfDrug to ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl2" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl2">Royalty percentage received on sales of drug</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnSalesOfDrug" xlink:to="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl2" xlink:title="label: RoyaltyPercentageReceivedOnSalesOfDrug to ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid" xlink:label="ProceedsFromSaleOfCommonStockIncludingPremiumPaid" xlink:title="ProceedsFromSaleOfCommonStockIncludingPremiumPaid" />
    <link:label xlink:type="resource" xlink:label="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl" xml:lang="en-US" id="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl">The cash inflow from the sale of common stock, including the premium paid for the purchase of common stock.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleOfCommonStockIncludingPremiumPaid" xlink:to="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl" xlink:title="label: ProceedsFromSaleOfCommonStockIncludingPremiumPaid to ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl1" xml:lang="en-US" id="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl1">Proceeds from sale of common stock, including premium paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleOfCommonStockIncludingPremiumPaid" xlink:to="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl1" xlink:title="label: ProceedsFromSaleOfCommonStockIncludingPremiumPaid to ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl2" xml:lang="en-US" id="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl2">Proceeds from sale of common stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleOfCommonStockIncludingPremiumPaid" xlink:to="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl2" xlink:title="label: ProceedsFromSaleOfCommonStockIncludingPremiumPaid to ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee" xlink:label="PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee" xlink:title="PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee_lbl" xml:lang="en-US" id="ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee_lbl">The percentage of license fees, milestone payments and royalties paid as sublicense fee under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee" xlink:to="ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee_lbl" xlink:title="label: PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee to ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee_lbl1" xml:lang="en-US" id="ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee_lbl1">Percentage of license fees, milestone payments and royalties paid as sublicense fee</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee" xlink:to="ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee_lbl1" xlink:title="label: PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee to ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee_lbl2" xml:lang="en-US" id="ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee_lbl2">Percentage of license fees, milestone payments and royalties paid as sublicense fee</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee" xlink:to="ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee_lbl2" xlink:title="label: PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee to ions_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_LicenseFeePaidPerDrug" xlink:label="LicenseFeePaidPerDrug" xlink:title="LicenseFeePaidPerDrug" />
    <link:label xlink:type="resource" xlink:label="ions_LicenseFeePaidPerDrug_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LicenseFeePaidPerDrug_lbl" xml:lang="en-US" id="ions_LicenseFeePaidPerDrug_lbl">The license fee payment receivable per drug under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicenseFeePaidPerDrug" xlink:to="ions_LicenseFeePaidPerDrug_lbl" xlink:title="label: LicenseFeePaidPerDrug to ions_LicenseFeePaidPerDrug_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LicenseFeePaidPerDrug_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LicenseFeePaidPerDrug_lbl1" xml:lang="en-US" id="ions_LicenseFeePaidPerDrug_lbl1">License fee receivable per drug</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicenseFeePaidPerDrug" xlink:to="ions_LicenseFeePaidPerDrug_lbl1" xlink:title="label: LicenseFeePaidPerDrug to ions_LicenseFeePaidPerDrug_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LicenseFeePaidPerDrug_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LicenseFeePaidPerDrug_lbl2" xml:lang="en-US" id="ions_LicenseFeePaidPerDrug_lbl2">License fee receivable per drug</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicenseFeePaidPerDrug" xlink:to="ions_LicenseFeePaidPerDrug_lbl2" xlink:title="label: LicenseFeePaidPerDrug to ions_LicenseFeePaidPerDrug_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl">Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Novartis to develop and commercialize AKCEA-APO(a)-L and AKCEA-APOCIII-L.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl2">Novartis [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture" xlink:label="PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture" xlink:title="PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture_lbl" xml:lang="en-US" id="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture_lbl">The potential premium received if common stock is purchased in the future under a Stock Purchase Agreement (SPA) in conjunction with the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture" xlink:to="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture_lbl" xlink:title="label: PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture to ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture_lbl1" xml:lang="en-US" id="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture_lbl1">Potential premium received if common stock is purchased in the future</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture" xlink:to="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture_lbl1" xlink:title="label: PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture to ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture_lbl2" xml:lang="en-US" id="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture_lbl2">Potential premium received if common stock is purchased in the future</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture" xlink:to="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture_lbl2" xlink:title="label: PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture to ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember" xlink:label="ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember" xlink:title="ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_lbl">Research and development (R&amp;D) services for AKCEA-APOCIII-L, an antisense therapy with the potential to significantly reduce cardiovascular risk in patients suffering from high levels of the lipoprotein ApoCIII.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember" xlink:to="ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_lbl" xlink:title="label: ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember to ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_lbl1">Research and Development Services for AKCEA-APOCIII-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember" xlink:to="ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_lbl1" xlink:title="label: ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember to ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_lbl2">R&amp;D Services for AKCEA-APOCIII-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember" xlink:to="ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_lbl2" xlink:title="label: ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember to ions_ResearchAndDevelopmentServicesForAKCEAAPOCIIILMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PremiumReceivedOnSharesIssued" xlink:label="PremiumReceivedOnSharesIssued" xlink:title="PremiumReceivedOnSharesIssued" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumReceivedOnSharesIssued_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PremiumReceivedOnSharesIssued_lbl" xml:lang="en-US" id="ions_PremiumReceivedOnSharesIssued_lbl">The total amount of the premium received over the trading price of common stock at the time of purchase.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumReceivedOnSharesIssued" xlink:to="ions_PremiumReceivedOnSharesIssued_lbl" xlink:title="label: PremiumReceivedOnSharesIssued to ions_PremiumReceivedOnSharesIssued_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumReceivedOnSharesIssued_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PremiumReceivedOnSharesIssued_lbl1" xml:lang="en-US" id="ions_PremiumReceivedOnSharesIssued_lbl1">Premium received on shares issued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumReceivedOnSharesIssued" xlink:to="ions_PremiumReceivedOnSharesIssued_lbl1" xlink:title="label: PremiumReceivedOnSharesIssued to ions_PremiumReceivedOnSharesIssued_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumReceivedOnSharesIssued_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PremiumReceivedOnSharesIssued_lbl2" xml:lang="en-US" id="ions_PremiumReceivedOnSharesIssued_lbl2">Premium received on shares issued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumReceivedOnSharesIssued" xlink:to="ions_PremiumReceivedOnSharesIssued_lbl2" xlink:title="label: PremiumReceivedOnSharesIssued to ions_PremiumReceivedOnSharesIssued_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember" xlink:label="ResearchAndDevelopmentServicesForAKCEAAPOALMember" xlink:title="ResearchAndDevelopmentServicesForAKCEAAPOALMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember_lbl">Research and development (R&amp;D) services for AKCEA-APO(a)-L, 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="ResearchAndDevelopmentServicesForAKCEAAPOALMember" xlink:to="ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember_lbl" xlink:title="label: ResearchAndDevelopmentServicesForAKCEAAPOALMember to ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember_lbl1">Research and Development Services for AKCEA-APO(a)-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForAKCEAAPOALMember" xlink:to="ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember_lbl1" xlink:title="label: ResearchAndDevelopmentServicesForAKCEAAPOALMember to ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember_lbl2">R&amp;D Services for AKCEA-APO(a)-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForAKCEAAPOALMember" xlink:to="ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember_lbl2" xlink:title="label: ResearchAndDevelopmentServicesForAKCEAAPOALMember to ions_ResearchAndDevelopmentServicesForAKCEAAPOALMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised" xlink:label="NumberOfDrugsWithExclusiveOptionThatCouldBeExercised" xlink:title="NumberOfDrugsWithExclusiveOptionThatCouldBeExercised" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised_lbl" xml:lang="en-US" id="ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised_lbl">The number of drugs with an exclusive option that could be exercised to develop and commercialize the drug and a license fee is paid under the collaboration agreement. The collaboration partner will assume all further global development, regulatory and commercialization activities for the licensed drug.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfDrugsWithExclusiveOptionThatCouldBeExercised" xlink:to="ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised_lbl" xlink:title="label: NumberOfDrugsWithExclusiveOptionThatCouldBeExercised to ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised_lbl1" xml:lang="en-US" id="ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised_lbl1">Number of drugs with exclusive option that could be exercised</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfDrugsWithExclusiveOptionThatCouldBeExercised" xlink:to="ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised_lbl1" xlink:title="label: NumberOfDrugsWithExclusiveOptionThatCouldBeExercised to ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised_lbl2" xml:lang="en-US" id="ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised_lbl2">Number of drugs with exclusive option that could be exercised</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfDrugsWithExclusiveOptionThatCouldBeExercised" xlink:to="ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised_lbl2" xlink:title="label: NumberOfDrugsWithExclusiveOptionThatCouldBeExercised to ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_IONISFXILMember" xlink:label="IONISFXILMember" xlink:title="IONISFXILMember" />
    <link:label xlink:type="resource" xlink:label="ions_IONISFXILMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IONISFXILMember_lbl1" xml:lang="en-US" id="ions_IONISFXILMember_lbl1">IONIS-FXI-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISFXILMember" xlink:to="ions_IONISFXILMember_lbl1" xlink:title="label: IONISFXILMember to ions_IONISFXILMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IONISFXILMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IONISFXILMember_lbl2" xml:lang="en-US" id="ions_IONISFXILMember_lbl2">IONIS-FXI-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISFXILMember" xlink:to="ions_IONISFXILMember_lbl2" xlink:title="label: IONISFXILMember to ions_IONISFXILMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_IONISFXIActivePharmaceuticalIngredientMember" xlink:label="IONISFXIActivePharmaceuticalIngredientMember" xlink:title="IONISFXIActivePharmaceuticalIngredientMember" />
    <link:label xlink:type="resource" xlink:label="ions_IONISFXIActivePharmaceuticalIngredientMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IONISFXIActivePharmaceuticalIngredientMember_lbl" xml:lang="en-US" id="ions_IONISFXIActivePharmaceuticalIngredientMember_lbl">Represents the active pharmaceutical ingredient, or API, for IONIS-FXI, an antisense drug designed to treat clotting disorders and the prevention of thrombosis.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISFXIActivePharmaceuticalIngredientMember" xlink:to="ions_IONISFXIActivePharmaceuticalIngredientMember_lbl" xlink:title="label: IONISFXIActivePharmaceuticalIngredientMember to ions_IONISFXIActivePharmaceuticalIngredientMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IONISFXIActivePharmaceuticalIngredientMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IONISFXIActivePharmaceuticalIngredientMember_lbl1" xml:lang="en-US" id="ions_IONISFXIActivePharmaceuticalIngredientMember_lbl1">IONIS-FXI Active Pharmaceutical Ingredient [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISFXIActivePharmaceuticalIngredientMember" xlink:to="ions_IONISFXIActivePharmaceuticalIngredientMember_lbl1" xlink:title="label: IONISFXIActivePharmaceuticalIngredientMember to ions_IONISFXIActivePharmaceuticalIngredientMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IONISFXIActivePharmaceuticalIngredientMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IONISFXIActivePharmaceuticalIngredientMember_lbl2" xml:lang="en-US" id="ions_IONISFXIActivePharmaceuticalIngredientMember_lbl2">IONIS-FXI API [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISFXIActivePharmaceuticalIngredientMember" xlink:to="ions_IONISFXIActivePharmaceuticalIngredientMember_lbl2" xlink:title="label: IONISFXIActivePharmaceuticalIngredientMember to ions_IONISFXIActivePharmaceuticalIngredientMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_ResearchAndDevelopmentServicesForIONISFXIMember" xlink:label="ResearchAndDevelopmentServicesForIONISFXIMember" xlink:title="ResearchAndDevelopmentServicesForIONISFXIMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForIONISFXIMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentServicesForIONISFXIMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForIONISFXIMember_lbl">Research and development (R&amp;D) services for IONIS-FXI, an antisense drug designed to treat clotting disorders and the prevention of thrombosis.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForIONISFXIMember" xlink:to="ions_ResearchAndDevelopmentServicesForIONISFXIMember_lbl" xlink:title="label: ResearchAndDevelopmentServicesForIONISFXIMember to ions_ResearchAndDevelopmentServicesForIONISFXIMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForIONISFXIMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentServicesForIONISFXIMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForIONISFXIMember_lbl1">Research and Development Services for IONIS-FXI [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForIONISFXIMember" xlink:to="ions_ResearchAndDevelopmentServicesForIONISFXIMember_lbl1" xlink:title="label: ResearchAndDevelopmentServicesForIONISFXIMember to ions_ResearchAndDevelopmentServicesForIONISFXIMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForIONISFXIMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentServicesForIONISFXIMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForIONISFXIMember_lbl2">R&amp;D Services for IONIS-FXI [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForIONISFXIMember" xlink:to="ions_ResearchAndDevelopmentServicesForIONISFXIMember_lbl2" xlink:title="label: ResearchAndDevelopmentServicesForIONISFXIMember to ions_ResearchAndDevelopmentServicesForIONISFXIMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_IONISFXIMember" xlink:label="IONISFXIMember" xlink:title="IONISFXIMember" />
    <link:label xlink:type="resource" xlink:label="ions_IONISFXIMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IONISFXIMember_lbl" xml:lang="en-US" id="ions_IONISFXIMember_lbl">IONIS-FXI is an antisense drug designed to treat clotting disorders and the prevention of thrombosis. It targets Factor XI, a clotting factor produced in the liver that is an important component of the coagulation pathway.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISFXIMember" xlink:to="ions_IONISFXIMember_lbl" xlink:title="label: IONISFXIMember to ions_IONISFXIMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IONISFXIMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IONISFXIMember_lbl1" xml:lang="en-US" id="ions_IONISFXIMember_lbl1">IONIS-FXI [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISFXIMember" xlink:to="ions_IONISFXIMember_lbl1" xlink:title="label: IONISFXIMember to ions_IONISFXIMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IONISFXIMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IONISFXIMember_lbl2" xml:lang="en-US" id="ions_IONISFXIMember_lbl2">IONIS-FXI [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISFXIMember" xlink:to="ions_IONISFXIMember_lbl2" xlink:title="label: IONISFXIMember to ions_IONISFXIMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement" xlink:label="RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement" xlink:title="RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl">The royalty percentage received on gross margins of drug(s) under the collaborative arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement" xlink:to="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl" xlink:title="label: RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement to ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl1">Royalty percentage received on gross margins of drugs under collaboration agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement" xlink:to="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement to ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl2" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl2">Royalty percentage received on gross margins of both drugs combined</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement" xlink:to="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl2" xlink:title="label: RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement to ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PaymentReceivedForAdvancingPrograms" xlink:label="PaymentReceivedForAdvancingPrograms" xlink:title="PaymentReceivedForAdvancingPrograms" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentReceivedForAdvancingPrograms_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PaymentReceivedForAdvancingPrograms_lbl" xml:lang="en-US" id="ions_PaymentReceivedForAdvancingPrograms_lbl">The amount of payments received during the period for advancing programs under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentReceivedForAdvancingPrograms" xlink:to="ions_PaymentReceivedForAdvancingPrograms_lbl" xlink:title="label: PaymentReceivedForAdvancingPrograms to ions_PaymentReceivedForAdvancingPrograms_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentReceivedForAdvancingPrograms_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PaymentReceivedForAdvancingPrograms_lbl1" xml:lang="en-US" id="ions_PaymentReceivedForAdvancingPrograms_lbl1">Payment received for advancing programs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentReceivedForAdvancingPrograms" xlink:to="ions_PaymentReceivedForAdvancingPrograms_lbl1" xlink:title="label: PaymentReceivedForAdvancingPrograms to ions_PaymentReceivedForAdvancingPrograms_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentReceivedForAdvancingPrograms_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PaymentReceivedForAdvancingPrograms_lbl2" xml:lang="en-US" id="ions_PaymentReceivedForAdvancingPrograms_lbl2">Payment received for advancing programs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentReceivedForAdvancingPrograms" xlink:to="ions_PaymentReceivedForAdvancingPrograms_lbl2" xlink:title="label: PaymentReceivedForAdvancingPrograms to ions_PaymentReceivedForAdvancingPrograms_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_ResearchAndDevelopmentServicesForIONISFXILMember" xlink:label="ResearchAndDevelopmentServicesForIONISFXILMember" xlink:title="ResearchAndDevelopmentServicesForIONISFXILMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForIONISFXILMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentServicesForIONISFXILMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForIONISFXILMember_lbl">Research and development (R&amp;D) services for IONIS-FXI-L.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForIONISFXILMember" xlink:to="ions_ResearchAndDevelopmentServicesForIONISFXILMember_lbl" xlink:title="label: ResearchAndDevelopmentServicesForIONISFXILMember to ions_ResearchAndDevelopmentServicesForIONISFXILMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForIONISFXILMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentServicesForIONISFXILMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForIONISFXILMember_lbl1">Research and Development Services for IONIS-FXI-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForIONISFXILMember" xlink:to="ions_ResearchAndDevelopmentServicesForIONISFXILMember_lbl1" xlink:title="label: ResearchAndDevelopmentServicesForIONISFXILMember to ions_ResearchAndDevelopmentServicesForIONISFXILMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForIONISFXILMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentServicesForIONISFXILMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForIONISFXILMember_lbl2">R&amp;D Services for IONIS-FXI-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForIONISFXILMember" xlink:to="ions_ResearchAndDevelopmentServicesForIONISFXILMember_lbl2" xlink:title="label: ResearchAndDevelopmentServicesForIONISFXILMember to ions_ResearchAndDevelopmentServicesForIONISFXILMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_NumberOfSignificantPartners" xlink:label="NumberOfSignificantPartners" xlink:title="NumberOfSignificantPartners" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantPartners_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfSignificantPartners_lbl" xml:lang="en-US" id="ions_NumberOfSignificantPartners_lbl">Represents the number of significant partners.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantPartners" xlink:to="ions_NumberOfSignificantPartners_lbl" xlink:title="label: NumberOfSignificantPartners to ions_NumberOfSignificantPartners_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantPartners_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfSignificantPartners_lbl1" xml:lang="en-US" id="ions_NumberOfSignificantPartners_lbl1">Number of Significant Partners</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantPartners" xlink:to="ions_NumberOfSignificantPartners_lbl1" xlink:title="label: NumberOfSignificantPartners to ions_NumberOfSignificantPartners_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantPartners_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfSignificantPartners_lbl2" xml:lang="en-US" id="ions_NumberOfSignificantPartners_lbl2">Number of significant partners</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantPartners" xlink:to="ions_NumberOfSignificantPartners_lbl2" xlink:title="label: NumberOfSignificantPartners to ions_NumberOfSignificantPartners_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_SignificantPartnersMember" xlink:label="SignificantPartnersMember" xlink:title="SignificantPartnersMember" />
    <link:label xlink:type="resource" xlink:label="ions_SignificantPartnersMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SignificantPartnersMember_lbl" xml:lang="en-US" id="ions_SignificantPartnersMember_lbl">Significant corporate partners and leading global pharmaceutical companies that are working alongside the Company to develop the Company's drugs, advance the Company's technology, and prepare to commercialize and sell the Company's drugs under collaborative arrangement and licensing agreements.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SignificantPartnersMember" xlink:to="ions_SignificantPartnersMember_lbl" xlink:title="label: SignificantPartnersMember to ions_SignificantPartnersMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SignificantPartnersMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SignificantPartnersMember_lbl1" xml:lang="en-US" id="ions_SignificantPartnersMember_lbl1">Significant Partners [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SignificantPartnersMember" xlink:to="ions_SignificantPartnersMember_lbl1" xlink:title="label: SignificantPartnersMember to ions_SignificantPartnersMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_SignificantPartnersMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SignificantPartnersMember_lbl2" xml:lang="en-US" id="ions_SignificantPartnersMember_lbl2">Significant Partners [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SignificantPartnersMember" xlink:to="ions_SignificantPartnersMember_lbl2" xlink:title="label: SignificantPartnersMember to ions_SignificantPartnersMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PartnerEMember" xlink:label="PartnerEMember" xlink:title="PartnerEMember" />
    <link:label xlink:type="resource" xlink:label="ions_PartnerEMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PartnerEMember_lbl" xml:lang="en-US" id="ions_PartnerEMember_lbl">Corporate partner and leading global pharmaceutical company that is working alongside the Company to develop the Company's drugs, advance the Company's technology, and prepare to commercialize and sell the Company's drugs under a collaborative arrangement and licensing agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PartnerEMember" xlink:to="ions_PartnerEMember_lbl" xlink:title="label: PartnerEMember to ions_PartnerEMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PartnerEMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PartnerEMember_lbl1" xml:lang="en-US" id="ions_PartnerEMember_lbl1">Partner E [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PartnerEMember" xlink:to="ions_PartnerEMember_lbl1" xlink:title="label: PartnerEMember to ions_PartnerEMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PartnerEMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PartnerEMember_lbl2" xml:lang="en-US" id="ions_PartnerEMember_lbl2">Partner E [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PartnerEMember" xlink:to="ions_PartnerEMember_lbl2" xlink:title="label: PartnerEMember to ions_PartnerEMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PartnerDMember" xlink:label="PartnerDMember" xlink:title="PartnerDMember" />
    <link:label xlink:type="resource" xlink:label="ions_PartnerDMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PartnerDMember_lbl" xml:lang="en-US" id="ions_PartnerDMember_lbl">Corporate partner and leading global pharmaceutical company that is working alongside the Company to develop the Company's drugs, advance the Company's technology, and prepare to commercialize and sell the Company's drugs under a collaborative arrangement and licensing agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PartnerDMember" xlink:to="ions_PartnerDMember_lbl" xlink:title="label: PartnerDMember to ions_PartnerDMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PartnerDMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PartnerDMember_lbl1" xml:lang="en-US" id="ions_PartnerDMember_lbl1">Partner D [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PartnerDMember" xlink:to="ions_PartnerDMember_lbl1" xlink:title="label: PartnerDMember to ions_PartnerDMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PartnerDMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PartnerDMember_lbl2" xml:lang="en-US" id="ions_PartnerDMember_lbl2">Partner D [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PartnerDMember" xlink:to="ions_PartnerDMember_lbl2" xlink:title="label: PartnerDMember to ions_PartnerDMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PartnerCMember" xlink:label="PartnerCMember" xlink:title="PartnerCMember" />
    <link:label xlink:type="resource" xlink:label="ions_PartnerCMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PartnerCMember_lbl" xml:lang="en-US" id="ions_PartnerCMember_lbl">Corporate partner and leading global pharmaceutical company that is working alongside the Company to develop the Company's drugs, advance the Company's technology, and prepare to commercialize and sell the Company's drugs under a collaborative arrangement and licensing agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PartnerCMember" xlink:to="ions_PartnerCMember_lbl" xlink:title="label: PartnerCMember to ions_PartnerCMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PartnerCMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PartnerCMember_lbl1" xml:lang="en-US" id="ions_PartnerCMember_lbl1">Partner C [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PartnerCMember" xlink:to="ions_PartnerCMember_lbl1" xlink:title="label: PartnerCMember to ions_PartnerCMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PartnerCMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PartnerCMember_lbl2" xml:lang="en-US" id="ions_PartnerCMember_lbl2">Partner C [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PartnerCMember" xlink:to="ions_PartnerCMember_lbl2" xlink:title="label: PartnerCMember to ions_PartnerCMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PartnerBMember" xlink:label="PartnerBMember" xlink:title="PartnerBMember" />
    <link:label xlink:type="resource" xlink:label="ions_PartnerBMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PartnerBMember_lbl" xml:lang="en-US" id="ions_PartnerBMember_lbl">Corporate partner and leading global pharmaceutical company that is working alongside the Company to develop the Company's drugs, advance the Company's technology, and prepare to commercialize and sell the Company's drugs under a collaborative arrangement and licensing agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PartnerBMember" xlink:to="ions_PartnerBMember_lbl" xlink:title="label: PartnerBMember to ions_PartnerBMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PartnerBMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PartnerBMember_lbl1" xml:lang="en-US" id="ions_PartnerBMember_lbl1">Partner B [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PartnerBMember" xlink:to="ions_PartnerBMember_lbl1" xlink:title="label: PartnerBMember to ions_PartnerBMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PartnerBMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PartnerBMember_lbl2" xml:lang="en-US" id="ions_PartnerBMember_lbl2">Partner B [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PartnerBMember" xlink:to="ions_PartnerBMember_lbl2" xlink:title="label: PartnerBMember to ions_PartnerBMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PartnerAMember" xlink:label="PartnerAMember" xlink:title="PartnerAMember" />
    <link:label xlink:type="resource" xlink:label="ions_PartnerAMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PartnerAMember_lbl" xml:lang="en-US" id="ions_PartnerAMember_lbl">Corporate partner and leading global pharmaceutical company that is working alongside the Company to develop the Company's drugs, advance the Company's technology, and prepare to commercialize and sell the Company's drugs under a collaborative arrangement and licensing agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PartnerAMember" xlink:to="ions_PartnerAMember_lbl" xlink:title="label: PartnerAMember to ions_PartnerAMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PartnerAMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PartnerAMember_lbl1" xml:lang="en-US" id="ions_PartnerAMember_lbl1">Partner A [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PartnerAMember" xlink:to="ions_PartnerAMember_lbl1" xlink:title="label: PartnerAMember to ions_PartnerAMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PartnerAMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PartnerAMember_lbl2" xml:lang="en-US" id="ions_PartnerAMember_lbl2">Partner A [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PartnerAMember" xlink:to="ions_PartnerAMember_lbl2" xlink:title="label: PartnerAMember to ions_PartnerAMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_SignificantPartnersAbstract" xlink:label="SignificantPartnersAbstract" xlink:title="SignificantPartnersAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_SignificantPartnersAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SignificantPartnersAbstract_lbl1" xml:lang="en-US" id="ions_SignificantPartnersAbstract_lbl1">Significant Partners [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SignificantPartnersAbstract" xlink:to="ions_SignificantPartnersAbstract_lbl1" xlink:title="label: SignificantPartnersAbstract to ions_SignificantPartnersAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_TermOfVariableRate" xlink:label="TermOfVariableRate" xlink:title="TermOfVariableRate" />
    <link:label xlink:type="resource" xlink:label="ions_TermOfVariableRate_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_TermOfVariableRate_lbl" xml:lang="en-US" id="ions_TermOfVariableRate_lbl">Term of the variable rate.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TermOfVariableRate" xlink:to="ions_TermOfVariableRate_lbl" xlink:title="label: TermOfVariableRate to ions_TermOfVariableRate_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_TermOfVariableRate_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_TermOfVariableRate_lbl1" xml:lang="en-US" id="ions_TermOfVariableRate_lbl1">Term of variable rate</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TermOfVariableRate" xlink:to="ions_TermOfVariableRate_lbl1" xlink:title="label: TermOfVariableRate to ions_TermOfVariableRate_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_MorganStanleyPrivateBankNationalAssociationMember" xlink:label="MorganStanleyPrivateBankNationalAssociationMember" xlink:title="MorganStanleyPrivateBankNationalAssociationMember" />
    <link:label xlink:type="resource" xlink:label="ions_MorganStanleyPrivateBankNationalAssociationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MorganStanleyPrivateBankNationalAssociationMember_lbl" xml:lang="en-US" id="ions_MorganStanleyPrivateBankNationalAssociationMember_lbl">Morgan Stanley Private Bank, National Association offers banking and credit products and services. The company was founded in 1996 and is based in Purchase, New York. Morgan Stanley Private Bank, National Association operates as a subsidiary of Morgan Stanley.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MorganStanleyPrivateBankNationalAssociationMember" xlink:to="ions_MorganStanleyPrivateBankNationalAssociationMember_lbl" xlink:title="label: MorganStanleyPrivateBankNationalAssociationMember to ions_MorganStanleyPrivateBankNationalAssociationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MorganStanleyPrivateBankNationalAssociationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MorganStanleyPrivateBankNationalAssociationMember_lbl1" xml:lang="en-US" id="ions_MorganStanleyPrivateBankNationalAssociationMember_lbl1">Morgan Stanley Private Bank, National Association [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MorganStanleyPrivateBankNationalAssociationMember" xlink:to="ions_MorganStanleyPrivateBankNationalAssociationMember_lbl1" xlink:title="label: MorganStanleyPrivateBankNationalAssociationMember to ions_MorganStanleyPrivateBankNationalAssociationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MorganStanleyPrivateBankNationalAssociationMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MorganStanleyPrivateBankNationalAssociationMember_lbl2" xml:lang="en-US" id="ions_MorganStanleyPrivateBankNationalAssociationMember_lbl2">Morgan Stanley [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MorganStanleyPrivateBankNationalAssociationMember" xlink:to="ions_MorganStanleyPrivateBankNationalAssociationMember_lbl2" xlink:title="label: MorganStanleyPrivateBankNationalAssociationMember to ions_MorganStanleyPrivateBankNationalAssociationMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_FixedRateNoteWithMorganStanleyMember" xlink:label="FixedRateNoteWithMorganStanleyMember" xlink:title="FixedRateNoteWithMorganStanleyMember" />
    <link:label xlink:type="resource" xlink:label="ions_FixedRateNoteWithMorganStanleyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_FixedRateNoteWithMorganStanleyMember_lbl" xml:lang="en-US" id="ions_FixedRateNoteWithMorganStanleyMember_lbl">Fixed rate note with Morgan Stanley Private Bank, National Association under a five-year revolving credit agreement dated June 16, 2015 and amended February 24, 2016.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FixedRateNoteWithMorganStanleyMember" xlink:to="ions_FixedRateNoteWithMorganStanleyMember_lbl" xlink:title="label: FixedRateNoteWithMorganStanleyMember to ions_FixedRateNoteWithMorganStanleyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_FixedRateNoteWithMorganStanleyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_FixedRateNoteWithMorganStanleyMember_lbl1" xml:lang="en-US" id="ions_FixedRateNoteWithMorganStanleyMember_lbl1">Fixed Rate Note with Morgan Stanley [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FixedRateNoteWithMorganStanleyMember" xlink:to="ions_FixedRateNoteWithMorganStanleyMember_lbl1" xlink:title="label: FixedRateNoteWithMorganStanleyMember to ions_FixedRateNoteWithMorganStanleyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_FixedRateNoteWithMorganStanleyMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_FixedRateNoteWithMorganStanleyMember_lbl2" xml:lang="en-US" id="ions_FixedRateNoteWithMorganStanleyMember_lbl2">Fixed Rate Note with Morgan Stanley [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FixedRateNoteWithMorganStanleyMember" xlink:to="ions_FixedRateNoteWithMorganStanleyMember_lbl2" xlink:title="label: FixedRateNoteWithMorganStanleyMember to ions_FixedRateNoteWithMorganStanleyMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_ConvertibleSeniorNotes275PercentMember" xlink:label="ConvertibleSeniorNotes275PercentMember" xlink:title="ConvertibleSeniorNotes275PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes275PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes275PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes275PercentMember_lbl">2 3/4 percent convertible senior notes due October 2019.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes275PercentMember" xlink:to="ions_ConvertibleSeniorNotes275PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes275PercentMember to ions_ConvertibleSeniorNotes275PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes275PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes275PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes275PercentMember_lbl1">Convertible Senior Notes 2.75 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes275PercentMember" xlink:to="ions_ConvertibleSeniorNotes275PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes275PercentMember to ions_ConvertibleSeniorNotes275PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes275PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes275PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes275PercentMember_lbl2">2 3/4 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes275PercentMember" xlink:to="ions_ConvertibleSeniorNotes275PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes275PercentMember to ions_ConvertibleSeniorNotes275PercentMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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-20180930.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:to="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" xlink:title="label: IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan to ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" />
    <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</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-20180930.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-20180930.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 when TEGSEDI received marketing authorization in one or more countries or approval from a government agency, such as the Food and Drug Administration (FDA).</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 when TEGSEDI received marketing authorization in the U.S. (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-20180930.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-20180930.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-20180930.xsd#ions_NumberOfAntisenseDrugsInDevelopment" xlink:label="NumberOfAntisenseDrugsInDevelopment" xlink:title="NumberOfAntisenseDrugsInDevelopment" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAntisenseDrugsInDevelopment_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfAntisenseDrugsInDevelopment_lbl" xml:lang="en-US" id="ions_NumberOfAntisenseDrugsInDevelopment_lbl">The number of antisense drugs in development designed to reduce the production of viral proteins associated with hepatitis B virus, or HBV, infection under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAntisenseDrugsInDevelopment" xlink:to="ions_NumberOfAntisenseDrugsInDevelopment_lbl" xlink:title="label: NumberOfAntisenseDrugsInDevelopment to ions_NumberOfAntisenseDrugsInDevelopment_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAntisenseDrugsInDevelopment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfAntisenseDrugsInDevelopment_lbl1" xml:lang="en-US" id="ions_NumberOfAntisenseDrugsInDevelopment_lbl1">Number of antisense drugs in development</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAntisenseDrugsInDevelopment" xlink:to="ions_NumberOfAntisenseDrugsInDevelopment_lbl1" xlink:title="label: NumberOfAntisenseDrugsInDevelopment to ions_NumberOfAntisenseDrugsInDevelopment_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl">Represents information pertaining to the collaborative arrangement and licensing agreement entered into with GlaxoSmithKline (GSK) in March 2010 to discover and develop new drugs against targets for rare and serious diseases, including infectious diseases and some conditions causing blindness.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in March 2010 with GSK [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl2">GSK [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl">The maximum amount of payments receivable for license fees and substantive milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones to ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl1">Maximum amount of payments receivable for license fees and substantive milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones to ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl2">Maximum amount of payments receivable for license fees and substantive milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones to ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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-20180930.xsd#ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForCommercializationMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForCommercializationMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl">The maximum amount of payments receivable for commercialization milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForCommercializationMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForCommercializationMilestones to ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl1">Maximum amount of payments receivable for commercialization milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForCommercializationMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForCommercializationMilestones to ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl2">Maximum amount of payments receivable for commercialization milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForCommercializationMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableForCommercializationMilestones to ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_IONISHBVAndIONISHBVLMember" xlink:label="IONISHBVAndIONISHBVLMember" xlink:title="IONISHBVAndIONISHBVLMember" />
    <link:label xlink:type="resource" xlink:label="ions_IONISHBVAndIONISHBVLMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IONISHBVAndIONISHBVLMember_lbl" xml:lang="en-US" id="ions_IONISHBVAndIONISHBVLMember_lbl">IONIS-HBV and IONIS-HBV-L are two antisense drugs designed to reduce the production of viral proteins associated with hepatitis B virus, or HBV infection, a follow-on compound based on LICA technology.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISHBVAndIONISHBVLMember" xlink:to="ions_IONISHBVAndIONISHBVLMember_lbl" xlink:title="label: IONISHBVAndIONISHBVLMember to ions_IONISHBVAndIONISHBVLMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IONISHBVAndIONISHBVLMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IONISHBVAndIONISHBVLMember_lbl1" xml:lang="en-US" id="ions_IONISHBVAndIONISHBVLMember_lbl1">IONIS-HBV and IONIS-HBV-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISHBVAndIONISHBVLMember" xlink:to="ions_IONISHBVAndIONISHBVLMember_lbl1" xlink:title="label: IONISHBVAndIONISHBVLMember to ions_IONISHBVAndIONISHBVLMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_TEGSEDIMember" xlink:label="TEGSEDIMember" xlink:title="TEGSEDIMember" />
    <link:label xlink:type="resource" xlink:label="ions_TEGSEDIMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_TEGSEDIMember_lbl" xml:lang="en-US" id="ions_TEGSEDIMember_lbl">TEGSEDI (inotersen) is a Generation 2+ antisense drug to treat people with hereditary TTR amyloidosis, or hATTR, a rare, progressive, fatal disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TEGSEDIMember" xlink:to="ions_TEGSEDIMember_lbl" xlink:title="label: TEGSEDIMember to ions_TEGSEDIMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_TEGSEDIMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_TEGSEDIMember_lbl1" xml:lang="en-US" id="ions_TEGSEDIMember_lbl1">TEGSEDI [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TEGSEDIMember" xlink:to="ions_TEGSEDIMember_lbl1" xlink:title="label: TEGSEDIMember to ions_TEGSEDIMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_TEGSEDIMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_TEGSEDIMember_lbl2" xml:lang="en-US" id="ions_TEGSEDIMember_lbl2">TEGSEDI [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TEGSEDIMember" xlink:to="ions_TEGSEDIMember_lbl2" xlink:title="label: TEGSEDIMember to ions_TEGSEDIMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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>
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    <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>
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    <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>
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    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in January 2012 with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="ions-20180930.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember to ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl" />
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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_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember to ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl2">Bayer [Member]</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" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2">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_lbl2" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBayerMember to ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl2">Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Biogen Inc. in December 2017 to identify new antisense oligonucleotide drug candidates for the treatment of spinal muscular atrophy, or SMA.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in December 2017 with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl2">New Antisense Drugs for the Treatment of SMA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl3" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl3">SMA Collaboration with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl3" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_AstraZenecaPLCMember" xlink:label="AstraZenecaPLCMember" xlink:title="AstraZenecaPLCMember" />
    <link:label xlink:type="resource" xlink:label="ions_AstraZenecaPLCMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AstraZenecaPLCMember_lbl" xml:lang="en-US" id="ions_AstraZenecaPLCMember_lbl">AstraZeneca PLC is a British-Swedish multinational pharmaceutical and biopharmaceutical company.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstraZenecaPLCMember" xlink:to="ions_AstraZenecaPLCMember_lbl" xlink:title="label: AstraZenecaPLCMember to ions_AstraZenecaPLCMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AstraZenecaPLCMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AstraZenecaPLCMember_lbl1" xml:lang="en-US" id="ions_AstraZenecaPLCMember_lbl1">AstraZeneca PLC [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstraZenecaPLCMember" xlink:to="ions_AstraZenecaPLCMember_lbl1" xlink:title="label: AstraZenecaPLCMember to ions_AstraZenecaPLCMember_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstraZenecaPLCMember" xlink:to="ions_AstraZenecaPLCMember_lbl2" xlink:title="label: AstraZenecaPLCMember to ions_AstraZenecaPLCMember_lbl2" />
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    <link:label xlink:type="resource" xlink:label="ions_OtherPartnersMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OtherPartnersMember_lbl" xml:lang="en-US" id="ions_OtherPartnersMember_lbl">Other collaboration partners, excluding Biogen Inc. (Biogen) and AstraZeneca PLC (AstraZeneca).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherPartnersMember" xlink:to="ions_OtherPartnersMember_lbl" xlink:title="label: OtherPartnersMember to ions_OtherPartnersMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OtherPartnersMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OtherPartnersMember_lbl1" xml:lang="en-US" id="ions_OtherPartnersMember_lbl1">Other Partners [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherPartnersMember" xlink:to="ions_OtherPartnersMember_lbl1" xlink:title="label: OtherPartnersMember to ions_OtherPartnersMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OtherPartnersMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OtherPartnersMember_lbl2" xml:lang="en-US" id="ions_OtherPartnersMember_lbl2">Other Partners [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherPartnersMember" xlink:to="ions_OtherPartnersMember_lbl2" xlink:title="label: OtherPartnersMember to ions_OtherPartnersMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance" xlink:label="MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance" xlink:title="MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance_lbl" xml:lang="en-US" id="ions_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance_lbl">Milestone payment earned during the period and amortized to revenue over the period of performance.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance_lbl1" xml:lang="en-US" id="ions_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance_lbl1">Milestone payment earned and amortized over period of performance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance" xlink:to="ions_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance_lbl1" xlink:title="label: MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance to ions_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance_lbl2" xml:lang="en-US" id="ions_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance_lbl2">Milestone payment earned and amortized over period of performance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance" xlink:to="ions_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance_lbl2" xlink:title="label: MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance to ions_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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>
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    <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-20180930.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>
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    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_SublicenseRevenueMember" xlink:label="SublicenseRevenueMember" xlink:title="SublicenseRevenueMember" />
    <link:label xlink:type="resource" xlink:label="ions_SublicenseRevenueMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SublicenseRevenueMember_lbl" xml:lang="en-US" id="ions_SublicenseRevenueMember_lbl">Sublicense revenue received from Akcea Therapeutics, Inc. under their collaboration agreement with a strategic partner.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SublicenseRevenueMember" xlink:to="ions_SublicenseRevenueMember_lbl" xlink:title="label: SublicenseRevenueMember to ions_SublicenseRevenueMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SublicenseRevenueMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SublicenseRevenueMember_lbl1" xml:lang="en-US" id="ions_SublicenseRevenueMember_lbl1">Sublicense Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SublicenseRevenueMember" xlink:to="ions_SublicenseRevenueMember_lbl1" xlink:title="label: SublicenseRevenueMember to ions_SublicenseRevenueMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_SublicenseRevenueMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SublicenseRevenueMember_lbl2" xml:lang="en-US" id="ions_SublicenseRevenueMember_lbl2">Sublicense Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SublicenseRevenueMember" xlink:to="ions_SublicenseRevenueMember_lbl2" xlink:title="label: SublicenseRevenueMember to ions_SublicenseRevenueMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner" xlink:label="RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner" xlink:title="RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner_lbl">Royalty percentage received on the net sales of each drug in Latin America from the collaboration partner under the collaboration agreement.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner_lbl1">Royalty percentage received on net sales of each drug in Latin America from collaboration partner</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner to ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner_lbl2" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner_lbl2">Royalty percentage received on net sales of each drug in Latin America from PTC</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner_lbl2" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner to ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil" xlink:label="PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil" xlink:title="PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl" xml:lang="en-US" id="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl">Period of time before collaboration partner pays royalties on net sales of product after first commercial sale in Brazil, 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="PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil" xlink:to="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl" xlink:title="label: PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil to ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl1" xml:lang="en-US" id="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl1">Period before collaboration partner pays royalties on net sales of product after first commercial sale in Brazil</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil" xlink:to="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl1" xlink:title="label: PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil to ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl2" xml:lang="en-US" id="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl2">Period before PTC pays royalties on net sales of product after first commercial sale in Brazil</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil" xlink:to="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl2" xlink:title="label: PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil to ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties" xlink:label="RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties" xlink:title="RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl" xml:lang="en-US" id="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl">The minimum amount of revenue recognized in Latin America by the collaboration partner before paying royalties.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl1" xml:lang="en-US" id="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl1">Revenue recognized by collaboration partner in Latin America before paying royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties" xlink:to="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl1" xlink:title="label: RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties to ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl2" xml:lang="en-US" id="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl2">Minimum revenue recognized in Latin America by PTC before paying royalties</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember_lbl">Represents information pertaining to the collaborative arrangement entered into with PTC Therapeutics by Akcea Therapeutics, Inc. in August 2018 to commercialize TEGSEDI and WAYLIVRA in Latin America.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in August 2018 with PTC Therapeutics [Member]</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval" xlink:label="PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval" xlink:title="PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval_lbl" xml:lang="en-US" id="ions_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval_lbl">The amount of the payment receivable under the license agreement to be received on the earlier of approval by the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA) under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval" xlink:to="ions_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval_lbl" xlink:title="label: PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval to ions_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval_lbl1" xml:lang="en-US" id="ions_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval_lbl1">Payment receivable under license agreement to be paid after approval</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval" xlink:to="ions_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval_lbl1" xlink:title="label: PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval to ions_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval" xlink:to="ions_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval_lbl2" xlink:title="label: PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval to ions_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones" xlink:label="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones" xlink:title="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl">The maximum amount of payments receivable per drug or program for regulatory milestone payments under the collaboration agreement.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl1">Maximum amount of payments receivable per drug or program for regulatory milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl2">Maximum amount of payments receivable per program for regulatory milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl3" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl3">Maximum amount of payments receivable per drug for regulatory milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl3" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PaymentReceivableUnderLicenseAgreement" xlink:label="PaymentReceivableUnderLicenseAgreement" xlink:title="PaymentReceivableUnderLicenseAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentReceivableUnderLicenseAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PaymentReceivableUnderLicenseAgreement_lbl" xml:lang="en-US" id="ions_PaymentReceivableUnderLicenseAgreement_lbl">The amount of payments expected to be received under the license agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentReceivableUnderLicenseAgreement" xlink:to="ions_PaymentReceivableUnderLicenseAgreement_lbl" xlink:title="label: PaymentReceivableUnderLicenseAgreement to ions_PaymentReceivableUnderLicenseAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentReceivableUnderLicenseAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PaymentReceivableUnderLicenseAgreement_lbl1" xml:lang="en-US" id="ions_PaymentReceivableUnderLicenseAgreement_lbl1">Payment receivable under license agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentReceivableUnderLicenseAgreement" xlink:to="ions_PaymentReceivableUnderLicenseAgreement_lbl1" xlink:title="label: PaymentReceivableUnderLicenseAgreement to ions_PaymentReceivableUnderLicenseAgreement_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentReceivableUnderLicenseAgreement_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PaymentReceivableUnderLicenseAgreement_lbl2" xml:lang="en-US" id="ions_PaymentReceivableUnderLicenseAgreement_lbl2">Payment receivable under license agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentReceivableUnderLicenseAgreement" xlink:to="ions_PaymentReceivableUnderLicenseAgreement_lbl2" xlink:title="label: PaymentReceivableUnderLicenseAgreement to ions_PaymentReceivableUnderLicenseAgreement_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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-20180930.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SecuritiesWithMaturityOfOneYearOrLessMember" xlink:to="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl" xlink:title="label: SecuritiesWithMaturityOfOneYearOrLessMember to ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl" />
    <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-20180930.xsd#ions_PaymentToSettleFinancingLiabilityForLeasedFacility" xlink:label="PaymentToSettleFinancingLiabilityForLeasedFacility" xlink:title="PaymentToSettleFinancingLiabilityForLeasedFacility" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentToSettleFinancingLiabilityForLeasedFacility_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PaymentToSettleFinancingLiabilityForLeasedFacility_lbl" xml:lang="en-US" id="ions_PaymentToSettleFinancingLiabilityForLeasedFacility_lbl">The cash outflow paid to settle financing liability for leased facility.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentToSettleFinancingLiabilityForLeasedFacility" xlink:to="ions_PaymentToSettleFinancingLiabilityForLeasedFacility_lbl" xlink:title="label: PaymentToSettleFinancingLiabilityForLeasedFacility to ions_PaymentToSettleFinancingLiabilityForLeasedFacility_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentToSettleFinancingLiabilityForLeasedFacility_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PaymentToSettleFinancingLiabilityForLeasedFacility_lbl1" xml:lang="en-US" id="ions_PaymentToSettleFinancingLiabilityForLeasedFacility_lbl1">Payment to settle financing liability for leased facility</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentToSettleFinancingLiabilityForLeasedFacility" xlink:to="ions_PaymentToSettleFinancingLiabilityForLeasedFacility_lbl1" xlink:title="label: PaymentToSettleFinancingLiabilityForLeasedFacility to ions_PaymentToSettleFinancingLiabilityForLeasedFacility_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentToSettleFinancingLiabilityForLeasedFacility_lbl2" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_PaymentToSettleFinancingLiabilityForLeasedFacility_lbl2" xml:lang="en-US" id="ions_PaymentToSettleFinancingLiabilityForLeasedFacility_lbl2">Payment to settle financing liability for leased facility</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentToSettleFinancingLiabilityForLeasedFacility" xlink:to="ions_PaymentToSettleFinancingLiabilityForLeasedFacility_lbl2" xlink:title="label: PaymentToSettleFinancingLiabilityForLeasedFacility to ions_PaymentToSettleFinancingLiabilityForLeasedFacility_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisInternationalAGMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NovartisInternationalAGMember_lbl2" xml:lang="en-US" id="ions_NovartisInternationalAGMember_lbl2">Novartis [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_lbl2" xlink:title="label: NovartisInternationalAGMember to ions_NovartisInternationalAGMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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-20180930.xsd#ions_AmortizationOfPatents" xlink:label="AmortizationOfPatents" xlink:title="AmortizationOfPatents" />
    <link:label xlink:type="resource" xlink:label="ions_AmortizationOfPatents_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AmortizationOfPatents_lbl" xml:lang="en-US" id="ions_AmortizationOfPatents_lbl">The aggregate expense that is charged against the earnings to allocate the cost of patents in a systematic and rational manner to the periods expected to benefit from such asset.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfPatents" xlink:to="ions_AmortizationOfPatents_lbl" xlink:title="label: AmortizationOfPatents to ions_AmortizationOfPatents_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AmortizationOfPatents_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AmortizationOfPatents_lbl1" xml:lang="en-US" id="ions_AmortizationOfPatents_lbl1">Amortization of Patents</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfPatents" xlink:to="ions_AmortizationOfPatents_lbl1" xlink:title="label: AmortizationOfPatents to ions_AmortizationOfPatents_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AmortizationOfPatents_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AmortizationOfPatents_lbl2" xml:lang="en-US" id="ions_AmortizationOfPatents_lbl2">Amortization of patents</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfPatents" xlink:to="ions_AmortizationOfPatents_lbl2" xlink:title="label: AmortizationOfPatents to ions_AmortizationOfPatents_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment" xlink:label="GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment" xlink:title="GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment" />
    <link:label xlink:type="resource" xlink:label="ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment_lbl" xml:lang="en-US" id="ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment_lbl">This item represents the gain (loss) realized on the sale of the Company's investment in Regulus Therapeutics Inc., classified as available-for-sale equity securities.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment" xlink:to="ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment_lbl" xlink:title="label: GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment to ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment_lbl1" xml:lang="en-US" id="ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment_lbl1">Gain (Loss) on Available-for-Sale Equity Securities, Significant Investment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment" xlink:to="ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment_lbl1" xlink:title="label: GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment to ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment_lbl2" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment_lbl2" xml:lang="en-US" id="ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment_lbl2">Gain on investment in Regulus Therapeutics, Inc.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment" xlink:to="ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment_lbl2" xlink:title="label: GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment to ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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-20180930.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" />
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    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_UnpaidDeferredOfferingCosts" xlink:label="UnpaidDeferredOfferingCosts" xlink:title="UnpaidDeferredOfferingCosts" />
    <link:label xlink:type="resource" xlink:label="ions_UnpaidDeferredOfferingCosts_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_UnpaidDeferredOfferingCosts_lbl" xml:lang="en-US" id="ions_UnpaidDeferredOfferingCosts_lbl">Future cash outflow to pay for deferred offering costs attributable to an offering of securities that have been incurred.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UnpaidDeferredOfferingCosts" xlink:to="ions_UnpaidDeferredOfferingCosts_lbl" xlink:title="label: UnpaidDeferredOfferingCosts to ions_UnpaidDeferredOfferingCosts_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_UnpaidDeferredOfferingCosts_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_UnpaidDeferredOfferingCosts_lbl1" xml:lang="en-US" id="ions_UnpaidDeferredOfferingCosts_lbl1">Unpaid Deferred Offering Costs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UnpaidDeferredOfferingCosts" xlink:to="ions_UnpaidDeferredOfferingCosts_lbl1" xlink:title="label: UnpaidDeferredOfferingCosts to ions_UnpaidDeferredOfferingCosts_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_UnpaidDeferredOfferingCosts_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_UnpaidDeferredOfferingCosts_lbl2" xml:lang="en-US" id="ions_UnpaidDeferredOfferingCosts_lbl2">Unpaid deferred offering costs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UnpaidDeferredOfferingCosts" xlink:to="ions_UnpaidDeferredOfferingCosts_lbl2" xlink:title="label: UnpaidDeferredOfferingCosts to ions_UnpaidDeferredOfferingCosts_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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>
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    <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>
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    <link:loc xlink:type="locator" xlink:href="ions-20180930.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/2009/role/negatedLabel" 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:label xlink:type="resource" xlink:label="ions_GainLossOnExtinguishmentOfFinancingLiability_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_GainLossOnExtinguishmentOfFinancingLiability_lbl3" xml:lang="en-US" id="ions_GainLossOnExtinguishmentOfFinancingLiability_lbl3">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_lbl3" xlink:title="label: GainLossOnExtinguishmentOfFinancingLiability to ions_GainLossOnExtinguishmentOfFinancingLiability_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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-20180930.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-20180930.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-20180930.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-20180930.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsIncMember" xlink:to="ions_AkceaTherapeuticsIncMember_lbl" xlink:title="label: AkceaTherapeuticsIncMember to ions_AkceaTherapeuticsIncMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsIncMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AkceaTherapeuticsIncMember_lbl1" xml:lang="en-US" id="ions_AkceaTherapeuticsIncMember_lbl1">Akcea Therapeutics, Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsIncMember" xlink:to="ions_AkceaTherapeuticsIncMember_lbl1" xlink:title="label: AkceaTherapeuticsIncMember to ions_AkceaTherapeuticsIncMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsIncMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AkceaTherapeuticsIncMember_lbl2" xml:lang="en-US" id="ions_AkceaTherapeuticsIncMember_lbl2">Akcea [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsIncMember" xlink:to="ions_AkceaTherapeuticsIncMember_lbl2" xlink:title="label: AkceaTherapeuticsIncMember to ions_AkceaTherapeuticsIncMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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-20180930.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-20180930.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>
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    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl2">1 Percent Convertible Senior Notes [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20180930.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>
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    <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>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange3" xlink:to="ions_MaximumContractMaturityPeriodRange3_lbl2" xlink:title="label: MaximumContractMaturityPeriodRange3 to ions_MaximumContractMaturityPeriodRange3_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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>
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    <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-20180930.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-20180930.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>
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    <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>
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    <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-20180930.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature beyond one year but within two years of the balance sheet date.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, after One Through Two Years, Percentage</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2">After one year but within two years</link:label>
    <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-20180930.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl">The aggregate percentage of all available-for-sale debt securities, regardless of maturity.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1">Available-for-sale Securities, Debt Maturities, Total, Percentage</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature within two years of the balance sheet date.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, within Two Years, Percentage</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2">Percentage of available-for-sale securities with a maturity of less than two years</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" />
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    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:label="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" />
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    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_LicensingAndOtherRoyaltiesMember" xlink:label="LicensingAndOtherRoyaltiesMember" xlink:title="LicensingAndOtherRoyaltiesMember" />
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    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LongTermObligationsNoncurrent_lbl1" xml:lang="en-US" id="ions_LongTermObligationsNoncurrent_lbl1">Long-term Obligations, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsNoncurrent" xlink:to="ions_LongTermObligationsNoncurrent_lbl1" xlink:title="label: LongTermObligationsNoncurrent to ions_LongTermObligationsNoncurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsNoncurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LongTermObligationsNoncurrent_lbl2" xml:lang="en-US" id="ions_LongTermObligationsNoncurrent_lbl2">Long-term obligations, less current portion</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsNoncurrent" xlink:to="ions_LongTermObligationsNoncurrent_lbl2" xlink:title="label: LongTermObligationsNoncurrent to ions_LongTermObligationsNoncurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:label="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:title="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl">The number of separate performance obligations under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:to="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" xlink:title="label: RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1">Revenue from Contract with Customer, Number of separate performance obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:to="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" xlink:title="label: RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl2" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl2">Number of separate performance obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:to="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl2" xlink:title="label: RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:label="PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:title="PaymentsIncludedInTransactionPriceForPerformanceObligation" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl" xml:lang="en-US" id="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl">Total payments received since inception of the collaboration agreement included in the transaction price for the performance obligation.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:to="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl" xlink:title="label: PaymentsIncludedInTransactionPriceForPerformanceObligation to ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl1" xml:lang="en-US" id="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl1">Payments included in transaction price for performance obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:to="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl1" xlink:title="label: PaymentsIncludedInTransactionPriceForPerformanceObligation to ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl2" xml:lang="en-US" id="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl2">Payments included in transaction price for performance obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:to="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl2" xlink:title="label: PaymentsIncludedInTransactionPriceForPerformanceObligation to ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_IONISAZ625Member" xlink:label="IONISAZ625Member" xlink:title="IONISAZ625Member" />
    <link:label xlink:type="resource" xlink:label="ions_IONISAZ625Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IONISAZ625Member_lbl" xml:lang="en-US" id="ions_IONISAZ625Member_lbl">A drug designed to inhibit an undisclosed target to treat patients with nonalcoholic steatohepatitis, or NASH.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISAZ625Member" xlink:to="ions_IONISAZ625Member_lbl" xlink:title="label: IONISAZ625Member to ions_IONISAZ625Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IONISAZ625Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IONISAZ625Member_lbl1" xml:lang="en-US" id="ions_IONISAZ625Member_lbl1">IONIS-AZ6-2.5 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISAZ625Member" xlink:to="ions_IONISAZ625Member_lbl1" xlink:title="label: IONISAZ625Member to ions_IONISAZ625Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IONISAZ625Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IONISAZ625Member_lbl2" xml:lang="en-US" id="ions_IONISAZ625Member_lbl2">IONIS-AZ6-2.5 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISAZ625Member" xlink:to="ions_IONISAZ625Member_lbl2" xlink:title="label: IONISAZ625Member to ions_IONISAZ625Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_IONISAZ525Member" xlink:label="IONISAZ525Member" xlink:title="IONISAZ525Member" />
    <link:label xlink:type="resource" xlink:label="ions_IONISAZ525Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IONISAZ525Member_lbl" xml:lang="en-US" id="ions_IONISAZ525Member_lbl">A drug designed to treat a genetically associated form of kidney disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISAZ525Member" xlink:to="ions_IONISAZ525Member_lbl" xlink:title="label: IONISAZ525Member to ions_IONISAZ525Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IONISAZ525Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IONISAZ525Member_lbl1" xml:lang="en-US" id="ions_IONISAZ525Member_lbl1">IONIS-AZ5-2.5 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISAZ525Member" xlink:to="ions_IONISAZ525Member_lbl1" xlink:title="label: IONISAZ525Member to ions_IONISAZ525Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IONISAZ525Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IONISAZ525Member_lbl2" xml:lang="en-US" id="ions_IONISAZ525Member_lbl2">IONIS-AZ5-2.5 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISAZ525Member" xlink:to="ions_IONISAZ525Member_lbl2" xlink:title="label: IONISAZ525Member to ions_IONISAZ525Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl">The maximum amount of payments receivable for regulatory milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForRegulatoryMilestones to ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl1">Maximum amount of payments receivable for regulatory milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForRegulatoryMilestones to ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl2">Maximum amount of payments receivable for regulatory milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableForRegulatoryMilestones to ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" xlink:label="MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" xlink:title="MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl" xml:lang="en-US" id="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl">The minimum amount of payments receivable for license fees and substantive milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" xlink:to="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl" xlink:title="label: MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones to ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl1" xml:lang="en-US" id="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl1">Minimum amount of payments receivable for license fees and substantive milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" xlink:to="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl1" xlink:title="label: MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones to ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl2" xml:lang="en-US" id="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl2">Minimum amount of payments receivable for license fees and substantive milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" xlink:to="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl2" xlink:title="label: MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones to ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl">The maximum amount of payments receivable for development milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForDevelopmentMilestones to ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl1">Maximum amount of payments receivable for development milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForDevelopmentMilestones to ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl2">Maximum amount of payments receivable for development milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableForDevelopmentMilestones to ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.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-20180930.xsd#ions_RevenueFromContractWithCustomerTransactionPrice" xlink:label="RevenueFromContractWithCustomerTransactionPrice" xlink:title="RevenueFromContractWithCustomerTransactionPrice" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPrice_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerTransactionPrice_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPrice_lbl">The amount of consideration the Company is eligible to earn under the collaboration agreement, including any variable consideration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPrice" xlink:to="ions_RevenueFromContractWithCustomerTransactionPrice_lbl" xlink:title="label: RevenueFromContractWithCustomerTransactionPrice to ions_RevenueFromContractWithCustomerTransactionPrice_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1">Revenue from Contract with Customer, Transaction Price</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPrice" xlink:to="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" xlink:title="label: RevenueFromContractWithCustomerTransactionPrice to ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPrice_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueFromContractWithCustomerTransactionPrice_lbl2" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPrice_lbl2">Transaction price</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPrice" xlink:to="ions_RevenueFromContractWithCustomerTransactionPrice_lbl2" xlink:title="label: RevenueFromContractWithCustomerTransactionPrice to ions_RevenueFromContractWithCustomerTransactionPrice_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20180930.xsd#ions_NumberOfObligationsFullySatisified" xlink:label="NumberOfObligationsFullySatisified" xlink:title="NumberOfObligationsFullySatisified" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfObligationsFullySatisified_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfObligationsFullySatisified_lbl" xml:lang="en-US" id="ions_NumberOfObligationsFullySatisified_lbl">The number of obligations fully satisfied under the collaboration agreement for which revenue is recognized over the period of performance.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfObligationsFullySatisified" xlink:to="ions_NumberOfObligationsFullySatisified_lbl" xlink:title="label: NumberOfObligationsFullySatisified to ions_NumberOfObligationsFullySatisified_lbl" />
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<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6842509584">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Document and Entity Information - shares<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Oct. 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_DocumentAndEntityInformationAbstract', window );"><strong>Document and Entity Information [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_dei_EntityRegistrantName', window );">Entity Registrant Name</a></td>
<td class="text">IONIS PHARMACEUTICALS INC<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityCentralIndexKey', window );">Entity Central Index Key</a></td>
<td class="text">0000874015<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_CurrentFiscalYearEndDate', window );">Current Fiscal Year End Date</a></td>
<td class="text">--12-31<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityFilerCategory', window );">Entity Filer Category</a></td>
<td class="text">Large Accelerated Filer<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntitySmallBusiness', window );">Entity Small Business</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
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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_dei_EntityEmergingGrowthCompany', window );">Entity Emerging Growth Company</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityExTransitionPeriod', window );">Entity Ex Transition Period</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityCommonStockSharesOutstanding', window );">Entity Common Stock, Shares Outstanding</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">137,571,510<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_dei_DocumentType', window );">Document Type</a></td>
<td class="text">10-Q<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_AmendmentFlag', window );">Amendment Flag</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_dei_DocumentPeriodEndDate', window );">Document Period End Date</a></td>
<td class="text">Sep. 30,  2018<span></span>
</td>
<td class="text">&#160;<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_dei_DocumentFiscalYearFocus', window );">Document Fiscal Year Focus</a></td>
<td class="text">2018<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 );">+ 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 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>
<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>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">
<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>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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<td>dei_</td>
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<td><strong> Balance Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentType">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 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">
<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 );">- 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>
<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 style="white-space:nowrap;">dei_EntityCentralIndexKey</td>
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<td>dei:centralIndexKeyItemType</td>
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<td><strong> Balance Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityCommonStockSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityCommonStockSharesOutstanding</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>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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityEmergingGrowthCompany</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>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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityExTransitionPeriod</td>
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<td><strong> Balance Type:</strong></td>
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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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<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>
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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>Sep. 30, 2018</div></th>
<th class="th"><div>Dec. 31, 2017</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_CashAndCashEquivalentsAtCarryingValue', window );">Cash and cash equivalents</a></td>
<td class="nump">$ 479,891<span></span>
</td>
<td class="nump">$ 129,630<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_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Short-term investments</a></td>
<td class="nump">1,479,098<span></span>
</td>
<td class="nump">893,085<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">14,732<span></span>
</td>
<td class="nump">62,955<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">8,378<span></span>
</td>
<td class="nump">9,982<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">97,125<span></span>
</td>
<td class="nump">73,082<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">2,079,224<span></span>
</td>
<td class="nump">1,168,734<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">132,003<span></span>
</td>
<td class="nump">121,907<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">24,027<span></span>
</td>
<td class="nump">22,004<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_OtherAssetsNoncurrent', window );">Deposits and other assets</a></td>
<td class="nump">12,659<span></span>
</td>
<td class="nump">10,129<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_Assets', window );">Total assets</a></td>
<td class="nump">2,247,913<span></span>
</td>
<td class="nump">1,322,774<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_LiabilitiesCurrentAbstract', window );"><strong>Current liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccountsPayableCurrent', window );">Accounts payable</a></td>
<td class="nump">13,576<span></span>
</td>
<td class="nump">24,886<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_EmployeeRelatedLiabilitiesCurrent', window );">Accrued compensation</a></td>
<td class="nump">24,259<span></span>
</td>
<td class="nump">25,151<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccruedLiabilitiesCurrent', window );">Accrued liabilities</a></td>
<td class="nump">50,786<span></span>
</td>
<td class="nump">66,618<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_LongTermObligationsCurrent', window );">Current portion of long-term obligations</a></td>
<td class="nump">14,472<span></span>
</td>
<td class="nump">1,621<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">157,145<span></span>
</td>
<td class="nump">125,336<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">260,238<span></span>
</td>
<td class="nump">243,612<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">523,384<span></span>
</td>
<td class="nump">108,026<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">559,184<span></span>
</td>
<td class="nump">533,111<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">5,138<span></span>
</td>
<td class="nump">12,974<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">59,825<span></span>
</td>
<td class="nump">59,771<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">1,407,769<span></span>
</td>
<td class="nump">957,494<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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, 137,506,203 and 124,976,373 shares issued and outstanding at September 30, 2018 and December 31, 2017, respectively</a></td>
<td class="nump">138<span></span>
</td>
<td class="nump">125<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdditionalPaidInCapitalCommonStock', window );">Additional paid-in capital</a></td>
<td class="nump">2,030,313<span></span>
</td>
<td class="nump">1,553,681<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">(32,532)<span></span>
</td>
<td class="num">(31,759)<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">(1,287,369)<span></span>
</td>
<td class="num">(1,241,034)<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">710,550<span></span>
</td>
<td class="nump">281,013<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">129,594<span></span>
</td>
<td class="nump">84,267<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">840,144<span></span>
</td>
<td class="nump">365,280<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">$ 2,247,913<span></span>
</td>
<td class="nump">$ 1,322,774<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LongTermObligationsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 obligations, including 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>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_LongTermObligationsCurrent</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_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>Carrying amount of long-term obligations due in the next twelve months or greater than the normal operating cycle, if longer, excluding convertible senior notes and a long-term financing liability for a leased facility.</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_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_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_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>
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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>
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<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>
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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 );">- 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>
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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:stringItemType</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_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>
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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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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6846532400">
<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>Sep. 30, 2018</div></th>
<th class="th"><div>Dec. 31, 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_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">137,506,203<span></span>
</td>
<td class="nump">124,976,373<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">137,506,203<span></span>
</td>
<td class="nump">124,976,373<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>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockParOrStatedValuePerShare">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
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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>num:perShareItemType</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>
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<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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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>xbrli:sharesItemType</td>
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<td>na</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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</table></div>
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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 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>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</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>
<td>instant</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>
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<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><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td>instant</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
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<a href="javascript:void(0);" 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>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_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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<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>
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</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>16
<FILENAME>R4.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;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6842687312">
<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>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 30, 2017</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 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_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 145,395<span></span>
</td>
<td class="nump">$ 118,314<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
<td class="nump">$ 346,387<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_OperatingExpensesAbstract', window );"><strong>Expenses:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl 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">95,255<span></span>
</td>
<td class="nump">80,214<span></span>
</td>
<td class="nump">301,153<span></span>
</td>
<td class="nump">246,358<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_SellingGeneralAndAdministrativeExpense', window );">Selling, general and administrative</a></td>
<td class="nump">68,712<span></span>
</td>
<td class="nump">26,788<span></span>
</td>
<td class="nump">178,563<span></span>
</td>
<td class="nump">62,782<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_OperatingExpenses', window );">Total operating expenses</a></td>
<td class="nump">163,967<span></span>
</td>
<td class="nump">107,002<span></span>
</td>
<td class="nump">479,716<span></span>
</td>
<td class="nump">309,140<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_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="num">(18,572)<span></span>
</td>
<td class="nump">11,312<span></span>
</td>
<td class="num">(72,157)<span></span>
</td>
<td class="nump">37,247<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_NonoperatingIncomeExpenseAbstract', window );"><strong>Other income (expense):</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_InvestmentIncomeNet', window );">Investment income</a></td>
<td class="nump">9,963<span></span>
</td>
<td class="nump">2,811<span></span>
</td>
<td class="nump">18,711<span></span>
</td>
<td class="nump">7,504<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_InterestExpense', window );">Interest expense</a></td>
<td class="num">(11,282)<span></span>
</td>
<td class="num">(10,825)<span></span>
</td>
<td class="num">(33,332)<span></span>
</td>
<td class="num">(33,966)<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_GainLossOnExtinguishmentOfFinancingLiability', window );">Loss on extinguishment of financing liability for leased facility</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(7,689)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(7,689)<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 income (expenses)</a></td>
<td class="num">(22)<span></span>
</td>
<td class="num">(2,141)<span></span>
</td>
<td class="num">(145)<span></span>
</td>
<td class="num">(3,528)<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 );">Loss before income tax expense</a></td>
<td class="num">(19,913)<span></span>
</td>
<td class="num">(6,532)<span></span>
</td>
<td class="num">(86,923)<span></span>
</td>
<td class="num">(432)<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">(452)<span></span>
</td>
<td class="num">(961)<span></span>
</td>
<td class="num">(824)<span></span>
</td>
<td class="num">(1,184)<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 loss</a></td>
<td class="num">(20,365)<span></span>
</td>
<td class="num">(7,493)<span></span>
</td>
<td class="num">(87,747)<span></span>
</td>
<td class="num">(1,616)<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 loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="nump">15,806<span></span>
</td>
<td class="nump">4,882<span></span>
</td>
<td class="nump">41,412<span></span>
</td>
<td class="nump">4,882<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="num">$ (4,559)<span></span>
</td>
<td class="num">$ (2,611)<span></span>
</td>
<td class="num">$ (46,335)<span></span>
</td>
<td class="nump">$ 3,266<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net income (loss) per share (in dollars per share)</a></td>
<td class="num">$ (0.03)<span></span>
</td>
<td class="num">$ (0.02)<span></span>
</td>
<td class="num">$ (0.33)<span></span>
</td>
<td class="nump">$ 0.13<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">143,314<span></span>
</td>
<td class="nump">124,370<span></span>
</td>
<td class="nump">132,518<span></span>
</td>
<td class="nump">123,746<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="num">$ (0.03)<span></span>
</td>
<td class="num">$ (0.02)<span></span>
</td>
<td class="num">$ (0.33)<span></span>
</td>
<td class="nump">$ 0.13<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">143,314<span></span>
</td>
<td class="nump">124,370<span></span>
</td>
<td class="nump">132,518<span></span>
</td>
<td class="nump">125,858<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>
</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">$ 82,756<span></span>
</td>
<td class="nump">$ 34,617<span></span>
</td>
<td class="nump">$ 181,975<span></span>
</td>
<td class="nump">$ 66,106<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>
</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>
<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">70,010<span></span>
</td>
<td class="nump">32,890<span></span>
</td>
<td class="nump">167,743<span></span>
</td>
<td class="nump">60,467<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>
</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">12,746<span></span>
</td>
<td class="nump">1,727<span></span>
</td>
<td class="nump">14,232<span></span>
</td>
<td class="nump">5,639<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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">$ 62,639<span></span>
</td>
<td class="nump">$ 83,697<span></span>
</td>
<td class="nump">$ 225,584<span></span>
</td>
<td class="nump">$ 280,281<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_GainLossOnExtinguishmentOfFinancingLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>Difference between the purchase price of the facility and the carrying value of our financing liability at the time of the purchase.</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_GainLossOnExtinguishmentOfFinancingLiability</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>
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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 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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</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_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>
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<tr>
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<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>num:perShareItemType</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_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>
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<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>num:perShareItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<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>
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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> Balance Type:</strong></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_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>
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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_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>
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<td><strong> Data Type:</strong></td>
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<tr>
<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
<td>duration</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>
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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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<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_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_OperatingExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>Generally recurring costs associated with normal operations except for the portion of these expenses which can be clearly related to production and included in cost of sales or services. Includes selling, general and administrative 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;">us-gaap_OperatingExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_OperatingExpensesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_OperatingExpensesAbstract</td>
</tr>
<tr>
<td style="padding-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>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenuesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_RevenuesAbstract</td>
</tr>
<tr>
<td style="padding-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_SellingGeneralAndAdministrativeExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 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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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6842647248">
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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>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 30, 2017</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 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_StatementOfIncomeAndComprehensiveIncomeAbstract', window );"><strong>CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<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 loss</a></td>
<td class="num">$ (20,365)<span></span>
</td>
<td class="num">$ (7,493)<span></span>
</td>
<td class="num">$ (87,747)<span></span>
</td>
<td class="num">$ (1,616)<span></span>
</td>
</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_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax', window );">Unrealized gains (losses) on debt securities, net of tax</a></td>
<td class="nump">133<span></span>
</td>
<td class="nump">215<span></span>
</td>
<td class="num">(834)<span></span>
</td>
<td class="nump">610<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_OtherComprehensiveIncomeLossReclassificationAdjustmentFromAOCIForSaleOfSecuritiesNetOfTax', window );">Reclassification adjustment for realized gains included in 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">(374)<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_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Currency translation adjustment</a></td>
<td class="num">(28)<span></span>
</td>
<td class="num">(42)<span></span>
</td>
<td class="nump">61<span></span>
</td>
<td class="num">(77)<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_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest', window );">Comprehensive loss</a></td>
<td class="num">(20,260)<span></span>
</td>
<td class="num">(7,320)<span></span>
</td>
<td class="num">(88,520)<span></span>
</td>
<td class="num">(1,457)<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_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest', window );">Comprehensive loss attributable to noncontrolling interests</a></td>
<td class="nump">15,797<span></span>
</td>
<td class="nump">3,952<span></span>
</td>
<td class="nump">41,455<span></span>
</td>
<td class="nump">3,952<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_ComprehensiveIncomeNetOfTax', window );">Comprehensive income (loss) attributable to Ionis Pharmaceuticals, Inc. stockholders</a></td>
<td class="num">$ (4,463)<span></span>
</td>
<td class="num">$ (3,368)<span></span>
</td>
<td class="num">$ (47,065)<span></span>
</td>
<td class="nump">$ 2,495<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ComprehensiveIncomeNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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, 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>
<td style="white-space:nowrap;">us-gaap_ComprehensiveIncomeNetOfTax</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 );">- 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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<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>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>
</tr>
<tr>
<td style="padding-right: 4px;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>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 reclassification adjustment from accumulated other comprehensive income for unrealized gain (loss) realized upon the sale of 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 15<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=d3e689-108580<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><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 50<br> -Paragraph 9<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=82897076&amp;loc=d3e27357-111563<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 17A<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL34724391-108580<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_OtherComprehensiveIncomeLossReclassificationAdjustmentFromAOCIForSaleOfSecuritiesNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Period Type:</strong></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>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProfitLoss</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 );">- 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;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6849607376">
<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">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 30, 2017</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_NetCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Operating activities:</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProfitLoss', window );">Net loss</a></td>
<td class="num">$ (87,747)<span></span>
</td>
<td class="num">$ (1,616)<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>
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<td class="text">&#160;<span></span>
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<tr class="ro">
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<td class="nump">7,650<span></span>
</td>
<td class="nump">6,138<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_AmortizationOfPatents', window );">Amortization of patents</a></td>
<td class="nump">1,356<span></span>
</td>
<td class="nump">1,216<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_AccretionAmortizationOfDiscountsAndPremiumsInvestments', window );">Amortization of premium on investments, net</a></td>
<td class="nump">791<span></span>
</td>
<td class="nump">5,227<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_AmortizationOfFinancingCosts', window );">Amortization of debt issuance costs</a></td>
<td class="nump">1,343<span></span>
</td>
<td class="nump">1,202<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">24,781<span></span>
</td>
<td class="nump">22,963<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AmortizationOfLeasedAsset', window );">Amortization of long-term financing liability for leased facility</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">3,659<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_ShareBasedCompensation', window );">Stock-based compensation expense</a></td>
<td class="nump">97,210<span></span>
</td>
<td class="nump">63,642<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_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment', window );">Gain on investment in Regulus Therapeutics, Inc.</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(374)<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_GainLossOnExtinguishmentOfFinancingLiability', window );">Loss on extinguishment of financing liability for leased facility</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">7,689<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_AssetImpairmentCharges', window );">Non-cash losses related to patents, licensing and property, plant and equipment</a></td>
<td class="nump">482<span></span>
</td>
<td class="num">(403)<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">48,223<span></span>
</td>
<td class="nump">65,119<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="nump">1,604<span></span>
</td>
<td class="num">(962)<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="num">(26,573)<span></span>
</td>
<td class="num">(34,866)<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">(13,606)<span></span>
</td>
<td class="num">(1,707)<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">(892)<span></span>
</td>
<td class="num">(8,999)<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="num">(14,392)<span></span>
</td>
<td class="num">(5,251)<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="nump">447,168<span></span>
</td>
<td class="nump">31,071<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">487,398<span></span>
</td>
<td class="nump">153,748<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">(1,156,335)<span></span>
</td>
<td class="num">(589,655)<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">568,517<span></span>
</td>
<td class="nump">313,860<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">(12,221)<span></span>
</td>
<td class="num">(26,502)<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">(3,317)<span></span>
</td>
<td class="num">(4,289)<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_ProceedsFromSaleOfEquityMethodInvestments', window );">Proceeds from the sale of Regulus Therapeutics stock</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">2,507<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_NetCashProvidedByUsedInInvestingActivities', window );">Net cash used in investing activities</a></td>
<td class="num">(603,356)<span></span>
</td>
<td class="num">(304,079)<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_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="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_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions', window );">Proceeds from equity awards</a></td>
<td class="nump">18,254<span></span>
</td>
<td class="nump">17,672<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_ProceedsFromIssuanceInitialPublicOffering', window );">Proceeds from the issuance of common stock from Akcea Therapeutics, Inc.'s initial public offering, net of underwriters' discount</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">110,438<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_ProceedsFromDebtNetOfIssuanceCosts', window );">Proceeds from building mortgage debt, net of issuance costs</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">59,750<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">(1,057)<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_ProceedsFromIssuanceOfPrivatePlacement', window );">Proceeds from the sale of Akcea Therapeutics, Inc. common stock to Novartis in a private placement</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">50,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_PaymentToSettleFinancingLiabilityForLeasedFacility', window );">Payment to settle financing liability for leased facility</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(80,133)<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_RepaymentsOfLongTermDebtAndCapitalSecurities', window );">Principal payments on debt and capital lease obligations</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(3,577)<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_NetCashProvidedByUsedInFinancingActivities', window );">Net cash provided by financing activities</a></td>
<td class="nump">466,219<span></span>
</td>
<td class="nump">224,830<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_CashAndCashEquivalentsPeriodIncreaseDecrease', window );">Net increase in cash and cash equivalents</a></td>
<td class="nump">350,261<span></span>
</td>
<td class="nump">74,499<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_CashAndCashEquivalentsAtCarryingValue', window );">Cash and cash equivalents at beginning of period</a></td>
<td class="nump">129,630<span></span>
</td>
<td class="nump">84,685<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_CashAndCashEquivalentsAtCarryingValue', window );">Cash and cash equivalents at end of period</a></td>
<td class="nump">479,891<span></span>
</td>
<td class="nump">159,184<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_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="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_InterestPaidNet', window );">Interest paid</a></td>
<td class="nump">5,434<span></span>
</td>
<td class="nump">4,020<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_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract', window );"><strong>Supplemental disclosures of non-cash investing and financing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NonCashCapitalAndPatentExpenditures', window );">Amounts accrued for capital and patent expenditures</a></td>
<td class="nump">2,296<span></span>
</td>
<td class="nump">3,475<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_CapitalExpendituresIncurredButNotYetPaid', window );">Purchases of property, plant and equipment included in long-term obligations</a></td>
<td class="nump">3,596<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_UnpaidDeferredOfferingCosts', window );">Unpaid deferred offering costs</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">638<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_NovartisInternationalAGMember', window );">Novartis [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_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_ProceedsFromIssuanceOfCommonStock', window );">Proceeds from issuance of common stock</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">71,737<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>
</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_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="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_ProceedsFromIssuanceOfCommonStock', window );">Proceeds from issuance of common stock</a></td>
<td class="nump">$ 447,965<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AmortizationOfPatents">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 that is charged against the earnings to allocate the cost of patents in a systematic and rational manner to the periods expected to benefit from such asset.</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_AmortizationOfPatents</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_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 gain (loss) realized on the sale of the Company's investment in Regulus Therapeutics Inc., classified as available-for-sale equity 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;">ions_GainLossOnAvailableForSaleEquitySecuritiesSignificantInvestment</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_GainLossOnExtinguishmentOfFinancingLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>Difference between the purchase price of the facility and the carrying value of our financing liability at the time of the purchase.</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_GainLossOnExtinguishmentOfFinancingLiability</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_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_PaymentToSettleFinancingLiabilityForLeasedFacility">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 paid to settle financing liability for leased facility.</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_PaymentToSettleFinancingLiabilityForLeasedFacility</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_ions_UnpaidDeferredOfferingCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 deferred offering costs attributable to an offering of securities 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_UnpaidDeferredOfferingCosts</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_AmortizationOfLeasedAsset">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 expense charged against earnings for the periodic recognition of capitalized leases. This element may apply to energy companies that lease mineral producing properties and to other enterprises that capitalize property, plant, or equipment obtained through capital leases.</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 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84164758&amp;loc=d3e45031-112735<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_AmortizationOfLeasedAsset</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_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>
</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_CapitalExpendituresIncurredButNotYetPaid">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 that have occurred.</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 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=98513485&amp;loc=d3e4332-108586<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=98513485&amp;loc=d3e4313-108586<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 3<br> -URI http://asc.fasb.org/extlink&amp;oid=98513485&amp;loc=d3e4304-108586<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_CapitalExpendituresIncurredButNotYetPaid</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_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_CashAndCashEquivalentsPeriodIncreaseDecrease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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. Cash and cash equivalents are the 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. Includes effect from exchange rate changes.</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_CashAndCashEquivalentsPeriodIncreaseDecrease</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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>
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</tr>
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</div></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 );">- 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>
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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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</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>
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</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
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</tr>
</table></div>
</div></td></tr>
</table>
<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>
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</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>
<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_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>
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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_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>
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<td><strong> Data Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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_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>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 associated with the acquisition of long-lived, physical assets that are used in the normal conduct of business to produce goods and services and not intended for resale; includes cash outflows to pay for construction of self-constructed assets.</p></div>
<a href="javascript:void(0);" onclick="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 (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3213-108585<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_PaymentsToAcquirePropertyPlantAndEquipment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromDebtNetOfIssuanceCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 inflow from additional borrowings, net of cash paid to third parties in connection with debt origination.</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 14<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3255-108585<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_ProceedsFromDebtNetOfIssuanceCosts</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_ProceedsFromIssuanceInitialPublicOffering">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 inflow associated with the amount received from entity's first offering of stock to the public.</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 14<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3255-108585<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_ProceedsFromIssuanceInitialPublicOffering</td>
</tr>
<tr>
<td style="padding-right: 4px;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>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfCommonStock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 inflow from the additional capital contribution to the entity.</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 14<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3255-108585<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_ProceedsFromIssuanceOfCommonStock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_ProceedsFromIssuanceOfPrivatePlacement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 inflow associated with the amount received from entity's raising of capital via private rather than public placement.</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 14<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3255-108585<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_ProceedsFromIssuanceOfPrivatePlacement</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 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>
<a href="javascript:void(0);" 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_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 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>
<a href="javascript:void(0);" 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_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromSaleOfEquityMethodInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 inflow associated with the sale of equity method investments, which are investments in joint ventures and entities in which the entity has an equity ownership interest normally of 20 to 50 percent and exercises significant influence.</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>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The cash outflow associated with security instruments that either represent a creditor or an ownership relationship with the holder of the investment security with a maturity of beyond one year or normal operating cycle, if longer.  Includes repayments of (a) debt, (b) capital lease obligations, (c) mandatory redeemable capital securities, and (d) any combination of (a), (b), or (c).</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;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6839344096">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Basis of Presentation<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_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock', window );">Basis of Presentation</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify;">1.&#160; Basis of Presentation</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended September 30, 2018 and 2017 on the same basis as the audited financial statements for the year ended December 31, 2017. 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, 2017 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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, which we formed in December 2014. </font>Prior to Akcea&#8217;s <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">initial public offering, or IPO,</font> 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 <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">68 percent </font>of Akcea. In the second and third 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. We reflected the increase in our ownership in these financial statements. In October 2018, we received an additional 1.7 million shares of Akcea&#8217;s stock when TEGSEDI received marketing authorization in the U.S., increasing our ownership to approximately 76 percent. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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; color: #000000; font-style: italic;">Significant Accounting Policies,</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> for further information related to our accounting for our investment in Akcea.</font></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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 );">- 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;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6829912736">
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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">9 Months Ended</th>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;">2.&#160; Significant Accounting Policies</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Revenue Recognition</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><u>Adoption of New Revenue Recognition Accounting Standard (Topic 606)</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">In May 2014, the FASB issued accounting guidance on the recognition of revenue from customers. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">This guidance supersedes the revenue recognition requirements we previously followed in Accounting Standards Codification, or ASC, Topic 605, </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;">Revenue Recognition</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">, or Topic 605, and created a new Topic 606, </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;">Revenue from Contracts with Customers</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">, or Topic 606. </font>Under Topic 606, an entity will recognize revenue when it transfers control of promised goods or services to customers in an amount that reflects what the entity expects to receive in exchange for the goods or services. Further, an entity will recognize revenue upon satisfying the performance obligation(s) under the related contract. We adopted Topic 606 on January 1, 2018 under the full retrospective approach, which required us to revise our prior period revenue. Under Topic 606, we were required to review all of our ongoing collaboration agreements in which we recognized revenue after January 1, 2016. We were required to assess what our revenue would have been for the period from January 1, 2016 to December 31, 2017 under Topic 606. As a result of this analysis, we determined that the cumulative revenue we would have recognized under Topic 606 decreased by $53.6 million. We recorded this amount as a cumulative adjustment to our accumulated deficit as of December 31, 2017. We have labeled our prior period financial statements &#8220;as revised&#8221; to indicate the change required under the accounting rules.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The following tables summarize the adjustments we were required to make to amounts we originally reported in 2017 to adopt Topic 606 (in thousands, except per share amounts):</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;">Condensed Consolidated Balance Sheet</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">At December 31, 2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#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;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">As Previously</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Reported under</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Topic 605</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Topic 606</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Adjustment</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;">SPINRAZA royalties</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">60,467</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">60,467</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;">Licensing and other royalty revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">4,983</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">656</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">5,639</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 17.75pt;">Total commercial revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">65,450</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">656</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">66,106</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;">Research and development revenue under collaborative agreements</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">269,917</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">10,364</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">280,281</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -9pt;">Total revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">335,367</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">11,020</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">346,387</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Income from operations</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">26,227</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">11,020</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">37,247</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Net income (loss)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(12,636</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">11,020</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(1,616</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; margin-left: 9pt; text-indent: -9pt;">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(8,716</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">11,982</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">3,266</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Net income (loss) per share, basic</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0.02</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0.11</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; 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This change resulted in an increase of $0.5 million and $27.9 million for the three and nine months ended September 30, 2017, respectively.</div></td></tr></table></div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>A change in how we calculate revenue for payments we are recognizing into revenue over time:</u></font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Under Topic 605, we amortized payments into revenue evenly over the period of our obligations. When we made a change to our estimated completion period, we recognized that change on a prospective basis. Under Topic 606, we are required to use an input method to determine the amount we amortize each reporting period. Each period, we review our &#8220;inputs&#8221; such as our level of effort expended, including the time we estimate it will take us to complete the activities, or costs incurred relative to the total expected inputs to satisfy the performance obligation. For certain collaborations, such as Bayer, Janssen and Novartis, the input method resulted in a change to the revenue we had previously recognized using a straight-line amortization method.</font><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;">This change resulted in a decrease of $4.0 million and $17.5 million for the three and nine months ended September 30, 2017, respectively.</font></div></td></tr></table></div><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">Our updated revenue recognition policy reflecting Topic 606 is as follows:</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"><u>Our Revenue Sources</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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 condensed consolidated balance sheet.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We expect to add product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 as a result of TEGSEDI&#8217;s approval in the U.S., EU and Canada. We will also recognize as commercial revenue future sales milestone payments and royalties we earn under our partnerships.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Research and development revenue under collaborative agreements</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">Our collaboration agreements are detailed in Note 6, <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements.</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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"><u>Steps to Recognize Revenue</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We use a five step process to determine the amount of revenue we should recognize and when we should recognize it. The five step process is as follows:</div><div><br /></div><div style="text-align: left;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;">1.</td><td style="width: auto; vertical-align: top; text-align: left;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;">Identify the contract</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; text-indent: 36pt;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</div><div><br /></div><div style="text-align: left;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: left;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">We and our partner approved the contract and we are both committed to perform our obligations;</div></td></tr></table></div><div style="text-align: left;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: left;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">We have identified our rights, our partner&#8217;s rights and the payment terms;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and</div></td></tr></table></div><div style="text-align: left;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: left;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">We believe collectability is probable.</div></td></tr></table></div><div><br /></div><div style="text-align: left;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;">2.</td><td style="width: auto; vertical-align: top; text-align: left;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;">Identify the performance obligations</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">Often times when we enter into a collaboration agreement in which we provide our partner with an option to license a drug 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 drug 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 drug or requests additional goods or services, then we identify a new performance obligation for that item.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;">3.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;">Determine the transaction price</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.</div><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;">4.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;">Allocate the transaction price</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Estimated future product sales;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Estimated royalties on future product sales;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Contractual milestone payments;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Expenses we expect to incur;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Income taxes; and</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">A discount rate.</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We typically estimate the selling price of R&amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;D services include:</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">The number of internal hours we estimate we will spend performing these services;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">The estimated cost of work we will perform;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">The estimated cost of work that we will contract with third parties to perform; and</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">The estimated cost of API we will use.</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">For purposes of determining the stand-alone selling price of the R&amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;">5.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;">Recognize revenue</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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; color: #000000;">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></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; text-indent: 36pt;">The following are examples of when we typically recognize revenue based on the types of payments we receive.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: left; text-indent: 36pt;"><u>Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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. Our accounting for SPINRAZA royalties did not change as a result of adopting Topic 606.</div><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: left; text-indent: 36pt;"><u>Research and development revenue under collaboration agreements:</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: left; text-indent: 36pt;"><u>Upfront Payments</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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 new SMA collaboration with Biogen, we received a $25 million upfront payment in December 2017. We allocated the upfront payment to our single performance obligation, R&amp;D services. We are amortizing the $25 million upfront payment using an input method over the estimated period of time we are providing R&amp;D services. Refer to <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Note 6, </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;">Collaborative Arrangements and Licensing Agreements</font>, for further discussion. Under Topic 605, we amortized upfront payments evenly over the period of our obligation.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: justify; text-indent: 36pt;"><u>Milestone Payments</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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 drug is approved by the applicable regulator. We will recognize sales based milestone payments in the period we achieve the milestone under the sales-based royalty exception allowed under accounting rules.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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. Under Topic 606, we allocated this payment to our R&amp;D services performance obligation. We are recognizing revenue from this milestone payment over our estimated period of performance. Under Topic 605, this milestone payment was recognized in full in the third quarter of 2017, which was the period in which we achieved the milestone event.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the milestone event. For example, in the third quarter of 2018, we earned a $10 million milestone payment when AstraZeneca initiated a Phase 1 study of IONIS-AZ4-2.5-L<sub>Rx</sub>. Our revenue recognition of milestone payments we earn based on our partners&#8217; activities did not change as a result of adopting Topic 606.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: justify; text-indent: 36pt;"><u>License Fees</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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 third quarter of 2018, we earned a $12 million license fee when our majority-owned affiliate, Akcea, <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">entered into an exclusive license agreement with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America</font>. Our recognition of license fees did not change as a result of adopting Topic 606.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;">Amendments to Agreements</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">1)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">2)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">If the goods and/or services are at a stand-alone selling price.</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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 standalone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> 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="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> 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="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> and to initiate development of IONIS-FXI-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">, 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="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> and IONIS-FXI-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">. 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="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">, 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; color: #000000;">Note 6, </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;">Collaborative Arrangements and Licensing Agreements</font>, for further discussion <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">of our accounting treatment for our Bayer collaboration. </font>Our allocation of the consideration we received for the Bayer amendment did not change as a result of adopting Topic 606. However, the method in which we are recognizing revenue related to our R&amp;D services performance obligation did change. We are amortizing revenue related to our R&amp;D services performance obligation using the input method under Topic 606.</div><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;">Multiple Agreements</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Whether the agreements were negotiated together with a single objective;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Whether the goods and/or services promised under the agreements are a single performance obligation.</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify;">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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; color: #000000;">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. Refer to Note 6, </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;">Collaborative Arrangements and Licensing Agreements</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> for further discussion of the accounting treatment for the 2018 strategic neurology collaboration with Biogen.</font></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left; margin-left: 54pt; text-indent: -18pt;">Contracts Receivable</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Our contracts receivable balance represents the amounts we have billed our partners for goods we have delivered or services we have performed that are due to us unconditionally. When we bill our partners 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</font>. Our contracts receivable balance as of December 31, 2017 did not change when we adopted Topic 606.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; margin-left: 54pt; text-indent: -18pt;">Unbilled SPINRAZA Royalties</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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>Our unbilled SPINRAZA royalties as of December 31, 2017 did not change when we adopted Topic 606.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left; margin-left: 54pt; text-indent: -18pt;">Deferred Revenue</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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 and nine months ended September 30, 2018, we recognized $37.2 million and $80.4 million of revenue from amounts that were in our beginning deferred revenue balances for those periods, respectively. During the three and nine months ended September 30, 2017, we recognized $31.6 million and $84.4 million of revenue from amounts that were in our beginning deferred revenue balances for those periods, respectively. 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text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">As Previously</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Reported under</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Topic 605</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Topic 606</div><div style="font-size: 10pt; 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color: #000000;">18,871</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">125,336</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">54,189</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; 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The increase was primarily related to the change in the accounting for certain milestone payments and the way in which we amortize payments. Under Topic 605, we previously recognized the majority of the milestone payments we earned in the period we achieved the milestone event, which did not impact our deferred revenue balance. Under Topic 606 we are now amortizing more milestone payments over the period of our performance obligation, which adds to our deferred revenue balance. Additionally, under Topic 605 we amortized payments evenly over the period of our obligation. Under Topic 606, we are required to use an input method to determine the amount we amortize each reporting period. The increase in deferred revenue relates to agreements with the following partners:</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$24.2 million from Biogen;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$15.9 million from AstraZeneca;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$11.8 from Novartis; and</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$2.3 million from other partners.</div></td></tr></table></div><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Noncontrolling Interest in Akcea Therapeutics, Inc.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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; color: #000000;">&#160;</font>of Akcea. In the second and third 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. We reflected this increase in our ownership percentage in these financial statements as an adjustment to noncontrolling interest. In October 2018, we received an additional 1.7 million shares of Akcea&#8217;s stock when TEGSEDI received marketing authorization in the U.S., increasing our ownership to approximately 76 percent. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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 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></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Cash, cash equivalents and investments</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At September 30, 2018, we held an equity investment in one publicly held company, 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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In January 2018, we adopted the amended accounting guidance related to the recognition, measurement, presentation, and disclosure of certain financial instruments. The amended guidance requires us to measure and record our equity investments at fair value. Additionally, the amended accounting guidance requires us to recognize the changes in fair value in our consolidated statement of operations, instead of through accumulated other comprehensive income. Prior to 2018, we accounted for our equity investments in privately held companies under the cost method of accounting. Under the amended guidance we account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. Our adoption of this guidance did not have an impact on our results.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Inventory valuation</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">We reflect our inventory on our 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 drugs because until we use these raw materials they have alternative future uses. We include in inventory raw material costs for drugs 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 drug. For example, if one of our drugs failed, we could use the raw materials for that drug to manufacture our other drugs. We expense these costs as R&amp;D expenses when we begin to manufacture API for a particular drug if the drug has not been approved for marketing by a regulatory agency.</div><div style="text-align: justify;"><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">We obtained the first regulatory approval for TEGSEDI in July 2018. At September 30, 2018 and December 31, 2017, 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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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 drugs and historical write-offs. We did not record any inventory write-offs for the nine months ended September 30, 2018 and 2017.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; margin-left: 36pt;">Research, development and patent expenses</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Long-lived assets</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We evaluate long-lived assets, which include property, plant and equipment 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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Use of estimates</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Basic and diluted net income (loss) per share</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Basic net income (loss) per share</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The calculation of total net income (loss) attributable to our common stockholders for the three and nine months ended September 30, 2018 and 2017 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. As a result of this calculation, our&#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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">Our basic net loss per share for the three months ended <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">September 30, 2018</font>, was calculated as follows (in thousands, except per share amounts):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;">Three months ended September 30, 2018</div></td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Weighted</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Average Shares</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Owned in Akcea</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; 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background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; 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background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; 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vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(110,680</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Ionis&#8217; stand-alone net income</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; 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background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; 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vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">132,518</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Basic net loss per share</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; 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font-weight: bold; color: #000000; text-align: left;">Three months ended September 30, 2017</div></td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Weighted</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Average Shares</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Owned in Akcea</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; 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font-weight: bold; color: #000000; text-align: center;">Akcea&#8217;s Net Loss</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: top;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Common shares</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">36,556</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(0.33</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(12,063</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Preferred shares</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">5,651</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(0.01</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(57</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Akcea&#8217;s net loss attributable to our ownership</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(12,120</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Ionis&#8217; stand-alone net income</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">10,144</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Net loss available to Ionis common stockholders</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(1,976</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Weighted average shares outstanding</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">124,370</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Basic net income per share</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(0.02</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr></table><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">Our basic net income per share for the <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">nine months ended September 30, 2017</font>, was calculated as follows (in thousands, except per share amounts):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;">Nine months ended September 30, 2017</div></td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; 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text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Common shares</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; 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padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Nine Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; 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vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">16,181</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">57,698</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">48,443</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; 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padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">5,291</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">39,512</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">15,199</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; 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text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">21,472</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">97,210</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">63,642</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td></tr></table><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">As of September 30, 2018, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options and RSUs was $139.5 million and $32.6 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 1.3 years and 1.6 years, respectively.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left; text-indent: 36pt;">Impact of recently issued accounting standards</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In February 2016, the FASB issued amended accounting guidance related to lease accounting, which will require us to record all leases with a term longer than one year on our balance sheet. When we record leases on our balance sheet under the new guidance, we will record a liability with a value equal to the present value of payments we will make over the life of the lease and an asset representing the underlying leased asset. The new accounting guidance requires us to determine if our leases are operating or financing leases. We will record expense for operating leases on a straight-line basis as an operating expense. If we determine a lease is a financing&#160;lease, we will record both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. The new lease standard is effective for annual and interim periods beginning after December 15, 2018, with early adoption permitted. We will adopt this guidance on January 1, 2019. We can choose from two methods of adoption. The first method requires us to reflect our leases on our balance sheet in the earliest comparative period presented in our financial statements. The second method requires us to reflect the impact of adoption on the date we adopt the new guidance and recognize a cumulative-effect adjustment to the opening balance of our accumulated deficit in that period. We are currently determining the method we will use to adopt the new guidance and assessing the effects the new guidance will have on our consolidated financial statements and disclosures.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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 consolidated financial statements and disclosures.</div><div><br /></div><div style="text-align: left;"><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In December 2017, the SEC staff issued guidance to address how companies should account for the Tax Act of 2017, or the Tax Act, when an entity does not have the necessary information to complete the accounting for the Tax Act and gives entities up to one year from the enactment of the Tax Act to finalize their amounts. We recognized provisional amounts in our 2017 financial statements and in these financial statements. The ultimate impact may differ materially from these provisional amounts due to, among other things, additional analysis, changes in our interpretations and assumptions, additional regulatory guidance that may be issued, and other actions we may take resulting from the Tax Act. We will assess and update our provisional amounts and disclosures, as necessary, at year end 2018.</div><div style="text-align: justify; text-indent: 36pt;"><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In February 2018, the FASB issued updated guidance for reclassification of tax effects from accumulated other comprehensive income (loss). The updated guidance gives entities an option to reclassify amounts included in accumulated other comprehensive income (loss) that under the Tax Act do not have a way to be relieved, and allows a one-time reclassification to retained earnings. The updated guidance is effective for all entities for fiscal years beginning after December 31, 2018, and interim periods within those fiscal years. Early adoption is permitted, and adoption is optional. We are currently assessing the effects this updated guidance could have on our consolidated financial statements and timing of potential adoption.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In June 2018, the FASB issued updated guidance to simplify the accounting for stock-based compensation expense for nonemployees. Specifically, we are now expensing grants to nonemployees in a similar manner as grants to employees and our Board of Directors. Previously, we had to re-value these grants at each reporting period to reflect the current fair value. Under the amended guidance, we value grants to nonemployees when we grant them and we will not adjust their value for future changes. We adopted this guidance in the second quarter of 2018 on a prospective basis. The updated guidance did not have a material impact to our financial results.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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 consolidated financial statements and timing of adoption.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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 anticipate we will adopt this updated guidance on January 1, 2019 and we do not expect it to have a significant impact on our disclosures.</div><div><br /></div></div><span></span>
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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6839373216">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<tr><th class="th"><div>Sep. 30, 2018</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>
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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_invest_InvestmentTextBlock', window );">Investments</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 0.1pt;">3.&#160; Investments</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">As of September 30, 2018, 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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The following table summarizes the contract maturity of the available-for-sale securities we held as of September 30, 2018:</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 60%; border-collapse: collapse;"><tr><td style="width: 83.04%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 46.8pt; text-indent: -9pt;">One year or less</div></td><td style="width: 16.96%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">80%</div></td></tr><tr><td style="width: 83.04%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 46.8pt; text-indent: -9pt;">After one year but within two years</div></td><td style="width: 16.96%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">15%</div></td></tr><tr><td style="width: 83.04%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 46.8pt; text-indent: -9pt;">After two years but within three years</div></td><td style="width: 16.96%; vertical-align: bottom; border-bottom: #000000 2px solid; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">5%</div></td></tr><tr><td style="width: 83.04%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 46.8pt; text-indent: -9pt;">Total</div></td><td style="width: 16.96%; vertical-align: bottom; border-bottom: #000000 4px double; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">100%</div></td></tr></table><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">As illustrated above, at September 30, 2018, 95 percent of our available-for-sale securities had a maturity of less than two years.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">At September 30, 2018, we had an ownership interest of less than 20 percent in four private companies and one public company 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 company is Antisense Therapeutics Limited.</div><div><br /></div><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The following is a summary of our investments (in thousands):</div><div style="text-align: left;"><br /></div><table cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"></td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="6" valign="bottom" style="vertical-align: bottom; 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text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 30%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Debt securities issued by U.S. government agencies</div></td><td valign="bottom" style="width: 7px; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">51</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; 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font-family: 'Times New Roman', Times, serif; color: #000000;">(139</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">26,862</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(139</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">159,093</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(278</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 30%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Debt securities issued by the U.S. Treasury</div></td><td valign="bottom" style="width: 7px; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">32</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">164,053</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(99</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">164,053</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(99</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 30%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td><td valign="bottom" style="width: 7px; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">48</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">25,687</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(191</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">51,747</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(690</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">77,434</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(881</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 30%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Total temporarily impaired securities</div></td><td valign="bottom" style="width: 7px; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">626</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">1,211,143</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(2,116</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">162,315</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(1,826</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">1,373,458</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 7%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(3,942</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</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;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6829901744">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fair Value Measurements<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<tr><th class="th"><div>Sep. 30, 2018</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_FairValueDisclosuresAbstract', window );"><strong>Fair Value Measurements [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_FairValueDisclosuresTextBlock', window );">Fair Value Measurements</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;">4.&#160; Fair Value Measurements</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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. During the nine months ended September 30, 2018, there were no transfers between our Level 1 and Level 2 investments. When we recognize transfers between levels of the fair value hierarchy, we recognize the transfer on the date the event or change in circumstances that caused the transfer occurs.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The following tables present the major security types we held at September 30, 2018 and December 31, 2017 that are regularly measured and carried at fair value. At September 30, 2018 and December 31, 2017, we did not have any financial instruments that we valued using Level 3 inputs. 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):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">At</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30, 2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Quoted Prices in</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Active Markets</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">(Level 1)</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; 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vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Corporate debt securities (2)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">1,078,960</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; 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vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">175,167</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; 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vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (3)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">80,658</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">80,658</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Total</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; 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font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">559,702</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">1,334,785</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td></tr></table><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">At</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">December 31, 2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Quoted Prices in</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Active Markets</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">(Level 1)</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Significant Other</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Observable Inputs</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">(Level 2)</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Cash equivalents (1)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; 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font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Other Fair Value Disclosures</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Novartis Future Stock Purchase</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In January 2017, we and Akcea entered into a SPA with Novartis. As part of the SPA, Novartis was required to purchase $50 million of Akcea&#8217;s common stock at the IPO price or our common stock at a premium if an IPO did not occur by April 2018. Therefore, at the inception of the SPA, we recorded a $5.0 million asset representing the fair value of the potential future premium we could have received if Novartis purchased our common stock. We determined the fair value of the future premium by calculating the value based on the stated premium in the SPA and estimating the probability of an Akcea IPO. We also included a <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">lack of marketability discount when we determined the fair value of the premium because we would have issued unregistered shares to Novartis if they had purchased our common stock. We measured this asset using Level 3 inputs and recorded it in other assets on our consolidated balance sheet. Because Akcea completed its IPO before April 2018, Novartis did not purchase additional shares of Ionis stock. 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font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; margin-left: 9pt; text-indent: -9pt;">Recurring fair value adjustment during the nine months ended September 30, 2017</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(5,035</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 88%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; margin-left: 9pt; text-indent: -9pt;">Ending balance of Level 3 instruments at September 30, 2017</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; 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We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.</div><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 the fair value of financial instruments (as defined), including financial assets and financial liabilities (collectively, as defined), and the measurements of those instruments as well as disclosures related to the fair value of non-financial assets and liabilities. Such disclosures about the financial instruments, assets, and liabilities would include: (1) the fair value of the required items together with their carrying amounts (as appropriate); (2) for items for which it is not practicable to estimate fair value, disclosure would include: (a) information pertinent to estimating fair value (including, carrying amount, effective interest rate, and maturity, and (b) the reasons why it is not practicable to estimate fair value; (3) significant concentrations of credit risk including: (a) information about the activity, region, or economic characteristics identifying a concentration, (b) the maximum amount of loss the entity is exposed to based on the gross fair value of the related item, (c) policy for requiring collateral or other security and information as to accessing such collateral or security, and (d) the nature and brief description of such collateral or security; (4) quantitative information about market risks and how such risks are managed; (5) for items measured on both a recurring and nonrecurring basis information regarding the inputs used to develop the fair value measurement; and (6) for items presented in the financial statement for which fair value measurement is elected: (a) information necessary to understand the reasons for the election, (b) discussion of the effect of fair value changes on earnings, (c) a description of [similar groups] items for which the election is made and the relation thereof to the balance sheet, the aggregate carrying value of items included in the balance sheet that are not eligible for the election; (7) all other required (as defined) and desired 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 820<br> -URI http://asc.fasb.org/topic&amp;trid=2155941<br></p></div>
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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6839332384">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Other Obligations<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<tr><th class="th"><div>Sep. 30, 2018</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_DebtDisclosureAbstract', window );"><strong>Other Obligations [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_DebtAndCapitalLeasesDisclosuresTextBlock', window );">Other Obligations</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;">5.&#160; Other Obligations</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Line of Credit Arrangement</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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, we can borrow up to a maximum of $30 million of revolving credit for general working capital purposes. Under the credit agreement interest is payable monthly in arrears on the outstanding principal at a borrowing rate based on our option of:</div><div><br /></div><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 58.5pt; vertical-align: top; align: right;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 36pt;">(i)</div></td><td style="width: auto; vertical-align: top;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify;">a floating rate equal to the one-month London Interbank Offered Rate, or LIBOR, in effect plus 1.25 percent per annum;</div></td></tr></table></div><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 58.5pt; vertical-align: top; align: right;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 36pt;">(ii)</div></td><td style="width: auto; vertical-align: top;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify;">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</div></td></tr></table></div><div><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 58.5pt; vertical-align: top; align: right;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 36pt;">(iii)</div></td><td style="width: auto; vertical-align: top;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify;">a fixed rate equal to the LIBOR swap rate during the period of the loan.</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">Additionally, we pay 0.25 percent per annum, payable quarterly in arrears, for any amount unused under the credit facility. As of September 30, 2018 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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The credit agreement includes customary affirmative and negative covenants and restrictions. We are in compliance with all covenants of the credit agreement.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Research and Development and Manufacturing Facilities</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">In July 2017, </font>we purchased the building that houses our primary R&amp;D facility and the building that houses our manufacturing facility for $79.4 million and $14.0 million, respectively. We financed the purchase of our primary R&amp;D facility and our 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 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.</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 debt and capital lease obligations can be reported. Information about short-term and long-term debt arrangements, which includes amounts of borrowings under each line of credit, note payable, commercial paper issue, bonds indenture, debenture issue, own-share lending arrangements and any other contractual agreement to repay funds, and about the underlying arrangements, rationale for a classification as long-term, including repayment terms, interest rates, collateral provided, restrictions on use of assets and activities, whether or not in compliance with debt covenants, and other matters important to users of the financial statements, such as the effects of refinancing and noncompliance with debt covenants. Also includes descriptions and amounts of capital leasing arrangements that consist of direct financing, sales type and leveraged leases. Disclosure may include the effect on the balance sheet and the income statement resulting from a change in lease classification for leases that at inception would have been classified differently had guidance been in effect at the inception of the original lease.</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> -URI http://asc.fasb.org/topic&amp;trid=2208923<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -URI http://asc.fasb.org/topic&amp;trid=2208564<br></p></div>
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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6829812272">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 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_CollaborativeArrangementsAndLicensingAgreementsAbstract', 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_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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;">6.&#160; Collaborative Arrangements and Licensing Agreements</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">Below, we have included all of our significant collaborations because we adopted Topic 606 on January 1, 2018. We have included new disclosures for each of our collaborations as required under Topic 606.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify;">Strategic Partnership</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Biogen</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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 drugs with Biogen's expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved drug to treat people with spinal muscular atrophy, or SMA. In</font> December 2017, we entered into a collaboration with Biogen to identify <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">new antisense drugs for the treatment of SMA</font>. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Additionally, we and Biogen are currently developing six other drugs to treat neurodegenerative diseases under these collaborations, including IONIS-SOD1</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> for ALS, IONIS-MAPT</font><sub style="color: #000000;">Rx </sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">for Alzheimer&#8217;s disease</font><sub style="color: #000000;">,</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> IONIS-C9</font><sub style="color: #000000;">Rx </sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">for ALS, and IONIS-BIIB6</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">, IONIS-BIIB7</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> and IONIS-BIIB8</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> to treat undisclosed neurodegenerative diseases. In addition to these drugs, we and Biogen are evaluating numerous additional targets to develop drugs to treat neurological diseases. Most recently, in April 2018, we entered into a new strategic collaboration for the treatment of neurological diseases with Biogen. From inception through September 2018, we have received over $1.9 billion from our Biogen collaborations, including $1 billion we received from Biogen in the second quarter of 2018 when we entered into the 2018 strategic neurology collaboration.</font></div><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; text-indent: 36pt;">SPINRAZA</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In January 2012, we entered into a collaboration agreement with Biogen to develop and commercialize SPINRAZA, an RNA-targeted therapy for the treatment of SMA. In December 2016, the FDA approved SPINRAZA for the treatment of SMA in pediatric and adult patients.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">From inception through September 2018, we earned $717 million in total revenue under our SPINRAZA collaboration, including $281 million in revenue from SPINRAZA royalties and $436 million in R&amp;D revenue. We are receiving tiered royalties ranging from 11 percent to 15 percent on any sales of SPINRAZA. We have exclusively in-licensed patents related to SPINRAZA from Cold Spring Harbor Laboratory and the University of Massachusetts. We pay Cold Spring Harbor Laboratory and the University of Massachusetts a low single digit royalty on sales of SPINRAZA. Biogen is responsible for all further global development, regulatory and commercialization activities and costs for SPINRAZA.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">Over the course of our SPINRAZA collaboration, we identified two performance obligations, which were to perform R&amp;D services and to deliver the SPINRAZA license to Biogen. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. We recognized revenue for our R&amp;D services performance obligation over our period of performance through December 2016. We recognized the $75 million license fee for SPINRAZA as revenue when we delivered the license to Biogen in July 2016 because Biogen 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 Biogen.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">We also earned additional milestone payments subsequent to delivering the license to Biogen that we recognized in full in the period each milestone payment became probable because we did not have a performance obligation related to each milestone payment. For example, we received $90 million of milestone payments for the approval of SPINRAZA in the EU and Japan in 2017 and recognized the full amounts into revenue in the period Biogen achieved the milestone events.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Neurology</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In December&#160;2012, we and Biogen entered into a collaboration agreement to develop and commercialize novel antisense drugs to up to three targets to treat neurodegenerative diseases. We are responsible for the development of each of the drugs through the completion of the initial Phase 2 clinical study for such drug. Biogen has the option to license a drug from each of the three programs through the completion of the first Phase 2 study for each program. We are currently advancing IONIS-MAPT<sub>Rx</sub> for Alzheimer&#8217;s disease under this collaboration. If Biogen exercises its option for a drug, it will assume all further global development, regulatory and commercialization responsibilities and costs for that drug.&#160;</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Under the terms of the agreement, we received an upfront payment of $30 million. Over the term of the collaboration, we are eligible to receive up to $210 million in a license fee and milestone payments per program, plus a mark-up on the cost estimate of the Phase 1 and 2 studies. The $210 million per program consists of up to $10 million in development milestone payments, plus a mark-up on the cost estimate of the Phase 1 and 2 studies and up to $130 million in milestone payments if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on sales of any drugs resulting from each of the three programs. From inception through September 2018, we have received $58 million in milestone payments and upfront fees under this collaboration. We will achieve the next payment of $7.5 </font>million if we continue to advance IONIS-MAPT<sub>Rx</sub>.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for Biogen. At inception, we determined the transaction price to be the $30 million upfront payment we received and allocated it to our single performance obligation. As we achieve milestone payments for our R&amp;D services, we include these amounts in our transaction price for our R&amp;D services performance obligation. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> currently estimate we will satisfy our performance obligation in </font>December 2020. From inception through <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">September 2018</font>, we have included $40 million in total payments in the transaction price for our R&amp;D services performance obligation.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; text-indent: 36pt;">2013 Strategic Neurology</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In September&#160;2013, we and Biogen entered into a long-term strategic relationship focused on applying antisense technology to advance the treatment of neurodegenerative diseases. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for neurological diseases and has the option to license drugs resulting from this collaboration. The exclusivity for neurological diseases will last through September 2019, and may be extended for any drug development programs Biogen is pursuing under the collaboration. We will usually be responsible for drug discovery and early development of antisense drugs and Biogen will have the option to license antisense drugs after Phase 2 proof of concept. In October 2016, we expanded our collaboration to include additional research activities we will perform. If Biogen exercises its option for a drug, it will assume all further global development, regulatory and commercialization responsibilities and costs for that drug. We are currently advancing five drugs, IONIS-SOD1<sub>Rx</sub>, IONIS-C9<sub>Rx</sub>, IONIS-BIIB6<sub>Rx</sub>, IONIS-BIIB7<sub>Rx</sub> and IONIS-BIIB8<sub>Rx</sub> under this collaboration. Biogen will be responsible for all of the drug discovery and development activities for drugs using other modalities.</div><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">Under the terms of the agreement, we received an upfront payment of $100 million and are eligible to receive milestone payments, license fees and royalty payments for all drugs developed through this collaboration, with the specific amounts dependent upon the modality of the molecule advanced by Biogen. For each antisense molecule that is chosen for drug discovery and development under this collaboration, we are eligible to receive up to approximately $260 million in a license fee and milestone payments per program. The $260 million per program consists of approximately $60 million in development milestones, including amounts related to the cost of clinical trials, and up to $130 million in milestone payments if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on sales from any antisense drugs developed under this collaboration. If Biogen chooses to advance drugs using other modalities, such as small molecules or monoclonal antibodies, we are eligible to receive up to $90 million in milestone payments per program. The $90 million per program consists of up to $35 million in development milestone payments and up to $55 million in milestone payments if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered single-digit royalties on sales from any drugs using non-antisense modalities developed under this collaboration. From inception through September 2018, we have received over $170 million in upfront fees, milestone payments and other payments under this collaboration, not including a $10 million milestone payment we earned in the third quarter of 2018 for Biogen&#8217;s initiation of a Phase 1 study for IONIS-C9<sub>Rx </sub>which we received in the fourth quarter of 2018. We will achieve the next payment of up to $10 million if we advance a program under this collaboration.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">At the commencement of our strategic neurology collaboration, we identified one performance obligation, which was to perform R&amp;D services for Biogen. At inception, we determined the transaction price to be the $100 million upfront payment we received and allocated it to our single performance obligation. As we achieve milestone payments for our R&amp;D services, we include these amounts in our transaction price for our R&amp;D services performance obligation. We are recognizing revenue for our R&amp;D services performance obligation based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">. </font>We<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> currently estimate we will satisfy our performance obligation in</font> September 2019. From inception through <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">September 2018</font>, we have included $145 million in total payments in the transaction price for our R&amp;D services performance obligation. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">In the third quarter of 2018, we earned a $10 million milestone payment when Biogen initiated a Phase 1 study of IONIS-C9</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">. We recognized this milestone payment in full in the third quarter because we do not have any performance obligations related to this milestone payment. Additionally, we concluded that the payment is not related to our R&amp;D services performance obligation.</font></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">New antisense drugs for the treatment of SMA</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">In December 2017, we entered into a collaboration agreement with Biogen to </font>identify <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">new antisense drugs for the treatment of SMA</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">. </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Biogen will have the option to license therapies arising out of this collaboration following the completion of preclinical studies. Upon licensing, Biogen </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">will be responsible for all further global development, regulatory and commercialization activities and costs for such therapies</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">. Under the collaboration agreement, we received a&#160;</font>$25 million<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#160;upfront payment in December 2017. We will receive development and regulatory milestone payments from Biogen if new drugs advance towards marketing approval. </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">In total over the term of our collaboration, we are eligible to receive up to $1.2 billion in license fees, milestone payments and other payments, including up to $80 million for the achievement of development milestones, up to $180 million for the achievement of commercialization milestones and up to $800 million for the achievement of sales milestones. In addition, we are eligible to receive tiered royalties </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">from the mid-teens to </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">mid-20 percent range </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">on net sales.</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> We will achieve the next payment of up to $60 million</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">for the license of a drug under this collaboration. </font></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for Biogen. We determined the transaction price to be the $25 million upfront payment we received when we entered into the collaboration. We allocated the transaction price to our single performance obligation. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> currently estimate we will satisfy our performance obligation in</font> December 2020.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; text-indent: 36pt;">2018 Strategic Neurology Collaboration</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In April 2018, we and Biogen entered into a new strategic collaboration to develop novel antisense drugs for a broad range of neurological diseases and entered into a SPA. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for these diseases for 10 years. We are responsible for the identification of antisense drug candidates based on selected targets, while Biogen will have the option to license therapies arising out of this collaboration and will be responsible for and pay for non-clinical studies, clinical development, manufacturing, and commercialization.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">In the second quarter of 2018, we received </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$1 billion from Biogen, comprised of $</font>625<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> million to purchase our stock at a 25 percent cash premium and $</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">375</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> million in an upfront payment. </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">We are eligible to receive up to $</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #222222;">270</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> million for each drug that achieves marketing approval. </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">In addition, we are eligible to receive tiered royalties </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">up to the 20 percent</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> range </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">on net sales.</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> We will achieve the next payment of $7.5 million if Biogen designates a target</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> under this collaboration. </font></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">At the commencement of this collaboration, </font>we identified one performance obligation, which was to perform R&amp;D services for Biogen.<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> We determined our transaction price to be $552 million, comprised of $375 million from the upfront payment and $177 million for the premium paid by Biogen for its purchase of our common stock.</font> We determined the fair value of the premium we received by using the stated premium in the SPA and applying a lack of marketability discount. 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font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Cardiac, Renal and Metabolic Diseases Collaboration</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">In July 2015, we and AstraZeneca formed a collaboration to discover and develop antisense therapies for treating cardiac, renal and metabolic diseases. Under our collaboration AstraZeneca has licensed three drugs from us. As part of the agreement, we granted AstraZeneca an exclusive license to IONIS-AZ4-2.5-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">, a drug we designed to treat cardiovascular disease and our first </font>drug that combines our Generation 2.5 and<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> LIgand-Conjugated Antisense, or LICA, technology. We also granted AstraZeneca the option to license a drug for each additional target advanced under this research collaboration. In February 2018, AstraZeneca licensed a second drug under our collaboration, IONIS-AZ5-2.5</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">, a drug we designed to </font>treat a genetically associated form of kidney disease<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">. In March 2018, AstraZeneca licensed a third drug under our collaboration, IONIS-AZ6-2.5-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">, a drug we designed to </font>inhibit an undisclosed target to treat patients with nonalcoholic steatohepatitis, or NASH<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">. AstraZeneca is responsible for all further global development, regulatory and commercialization activities and costs for IONIS-AZ4-2.5-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">, IONIS-AZ5-2.5</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> and</font><sub style="color: #000000;">&#160;</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">IONIS-AZ6-2.5-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> and any other future drugs AstraZeneca licenses.</font></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">Under the terms of the agreement, we received a $65 million upfront payment. We are eligible to receive license fees and milestone payments of up to more than $4 billion as drugs under this collaboration advance, including up to $1.1 billion for the achievement of development milestones and up to $2.9 billion for regulatory milestones. In addition, we are eligible to receive tiered royalties up to the low teens on sales from any product that AstraZeneca successfully commercializes under this collaboration agreement. From inception through September 2018, we have received over $165 million in upfront fees, license fees, milestone payments, and other payments under this collaboration, including a $10 million milestone payment we earned in the third quarter of 2018 when AstraZeneca initiated a Phase 1 trial for IONIS-AZ4-2.5-L<sub>Rx</sub>. We will achieve the next payment of $10 million under this collaboration if we advance a drug under this collaboration<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</font></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for AstraZeneca. We determined the transaction price to be the $65 million upfront payment we received and we allocated it to our single performance obligation. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy this performance obligation relative to our total effort expected to satisfy our performance obligation. We<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> currently estimate we will satisfy this performance obligation in</font> August 2021. As we achieve milestone payments for our R&amp;D services, we include these amounts in our transaction price for our R&amp;D services performance obligation. From inception through <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">September 2018</font>, we have included $90 million in payments in the transaction price for our R&amp;D services performance obligation.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">We identified separate performance obligations upon AstraZeneca&#8217;s license of IONIS-AZ5-2.5<sub>Rx</sub> and IONIS-AZ6-2.5-L<sub>Rx</sub> in the first quarter of 2018 because the licenses are distinct from our other performance obligation and each other. We recognized each $30 million license fee in the first quarter of 2018 because AstraZeneca had full use of the licenses without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the licenses after we delivered them to AstraZeneca.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In the third quarter of 2018, we earned a $10 million milestone payment when AstraZeneca initiated a Phase 1 study of IONIS-AZ4-2.5-L<sub>Rx</sub>. We recognized this milestone payment in full in the third quarter because we do not have any performance obligations related to this milestone payment. Additionally, we concluded that the payment is not related to our R&amp;D services performance obligation.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Oncology Collaboration</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">In December&#160;2012, we entered into a collaboration agreement with AstraZeneca to discover and develop antisense drugs to treat cancer.&#160;As part of the agreement, we granted AstraZeneca an exclusive license to develop and commercialize </font>danvatirsen (formerly <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">IONIS-STAT3-2.5</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">) for the treatment of cancer. AstraZeneca is now responsible for all global development, regulatory and commercialization activities for </font>danvatirsen<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">. We and AstraZeneca have evaluated </font>danvatirsen<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> in people with head and neck cancer, advanced lymphoma and advanced metastatic hepatocellular carcinoma. AstraZeneca is evaluating </font>danvatirsen<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> in combination with Imfinzi (durvalumab), AstraZeneca&#8217;s programmed death ligand, or PD-L1, blocking drug, in people with head and neck cancer, metastatic bladder cancer and metastatic non-small cell lung cancer. In addition, we and AstraZeneca established an oncology research program. AstraZeneca has the option to license drugs resulting from the program, and if AstraZeneca exercises its option for a drug, it will be responsible for all further global development, regulatory and commercialization activities and costs for such drug.</font></div><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Under the terms of this agreement, we received $31 million in upfront payments. We are eligible to receive milestone payments and license fees from AstraZeneca as programs advance in development. If AstraZeneca successfully develops </font>danvatirsen<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> and another drug under the research program, we could receive license fees and milestone payments of up to more than $450 million, including up to $152 million for the achievement of development milestones and up to $275 million for the achievement of regulatory milestones.&#160;In addition, we are eligible to receive tiered royalties up to the low to mid-teens on sales from any drugs resulting from these programs. From inception through September 2018, we have received $97.8 million in upfront fees, milestone payments, and other payments under this oncology collaboration, not including nearly $30 million in milestone payments we achieved when AstraZeneca advanced</font> two programs in the fourth quarter of 2018. We <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">will achieve the next payment of up to $25.0 million </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">if we advance a drug under our cancer research program with AstraZeneca.</font></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">At the commencement of this collaboration, we identified four performance obligations. We determined the transaction price to be the $31 million in upfront payments we received. We allocated the transaction price based on the estimated stand-alone selling price of each of our performance obligations and recognized the associated revenue over the period of our performance. We recognized revenue for three of our obligations over our period of performance, concluding in March 2014. Our remaining performance obligation was to perform R&amp;D services. We allocated $7.6 million to this performance obligation and recognized the associated revenue over the period of our performance, which ended in February 2018. 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color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;">R&amp;D revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">14.2</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; 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background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">4</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">21</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">4</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; 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color: #000000; text-align: justify; text-indent: 36pt;">In May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI<sub>Rx</sub> for the prevention of thrombosis. We were responsible for completing a Phase 2 study of IONIS-FXI<sub>Rx</sub> in people with end-stage renal disease on hemodialysis. Under the terms of the agreement, we received a $100 million upfront payment in the second quarter of 2015. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI<sub>Rx</sub> and to initiate development of IONIS-FXI-L<sub>Rx</sub>, which Bayer licensed. In conjunction with the decision to advance these programs, we received a $75 million payment from Bayer. We are conducting a Phase 2b study evaluating IONIS-FXI<sub>Rx</sub> in people with end-stage renal disease on hemodialysis to finalize dose selection. Additionally, we plan to develop IONIS-FXI-L<sub>Rx</sub> through Phase 1. Following these studies and Bayer's decision to further advance these programs, Bayer will be responsible for all global development, regulatory and commercialization activities and costs for both drugs.&#160;</div></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We are eligible to receive additional milestone payments as each drug advances toward the market. In total over the term of this collaboration, we are eligible to receive up to $385 million in license fees, milestone payments and other payments, including up to $125 million for the achievement of development milestones and up to $110 million for the achievement of commercialization milestones. In addition, we are eligible to receive tiered royalties in the low to high 20 percent range on gross margins of both drugs combined. From inception through September 2018, we have received over $175 million from our Bayer collaboration. We will achieve the next payment of $10 million if a program advances under this collaboration.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">At the commencement of this collaboration, we identified three performance obligations. We determined the transaction price to be the $100 million in upfront payment we received. We allocated the transaction price based on the relative stand-alone selling prices of each of our performance obligations and recognized the associated revenue as follows:</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognized $91.2 million for the exclusive license of IONIS-FXI<sub>Rx </sub>in May 2015 because Bayer <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">had full use of the license without any continuing involvement from us</font>.</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognized $4.3 million for the R&amp;D services for IONIS-FXI<sub>Rx</sub> over the period of our performance, which ended in November 2016.</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We allocated $4.5 million for API, which we are recognizing into revenue as we deliver the API.</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">In February 2017, when we amended our collaboration with Bayer, we identified two new performance obligations<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">, one for the license of IONIS-FXI-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> and one for R&amp;D services</font>. We determined the transaction price to be the $75 million payment. We allocated $64.9 million to <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">the license of IONIS-FXI-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> based on its estimated stand-alone selling price and recognized the associated revenue upon our delivery of the license in the first quarter of 2017. We allocated $10.1 million to our R&amp;D services performance obligation based on an estimated stand-alone selling price. </font>We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. 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Janssen has the option to license drugs from us through the designation of a development candidate for up to three programs. Prior to option exercise we are responsible for the discovery activities to identify a development candidate. If Janssen exercises an option for one of the programs, it will be responsible for the global development, regulatory and commercial activities under that program. Under the terms of the agreement, we received $35 million in upfront payments. We are eligible to receive up to more than $800 million in license fees and milestone payments for these programs, including up to $175 million for the achievement of development milestones, up to $440 million for the achievement of regulatory milestones and up to $180 million for the achievement of commercialization milestones. From inception through September 2018, we have received $75 million, including $15 million in license fees when Janssen licensed IONIS-JBI1-2.5<sub>Rx</sub> and IONIS-JBI2-2.5<sub>Rx</sub> from us in 2016 and 2017, respectively. We also received $5 million in January 2018 for the initiation of a Phase 1 study of IONIS-JBI1-2.5<sub>Rx </sub>in late 2017. In addition, we are eligible to receive tiered royalties up to the near teens on sales from any drugs resulting from this collaboration. We will achieve the next payment of $5 million if Janssen continues to advance a target under this collaboration.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for Janssen. We determined the transaction price to be the $35 million upfront payments we received. 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color: #000000; text-align: left;">&#160;</div></td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; 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vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">18.1</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Percentage of total revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">1</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; 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font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We did not have any deferred revenue from our relationship with Janssen at September 30, 2018 or December 31, 2017.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Roche</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; margin-left: 36pt;">Huntington's Disease</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In April&#160;2013, we formed an alliance with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, to develop treatments for Huntington's disease, or HD, based on our antisense technology. Roche had the option to license the drugs from us through the completion of the first Phase 1 trial. Under the agreement, we are responsible for the discovery and development of an antisense drug targeting huntingtin, or HTT, protein. We evaluated a drug targeting HTT, IONIS-HTT<sub>Rx</sub>, in a Phase 1/2a clinical study in people with early stage HD.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In December 2017, upon completion of the Phase 1/2a study, Roche exercised its option to license IONIS-HTT<sub>Rx </sub>and is now responsible for the global development, regulatory and commercialization activities for IONIS-HTT<sub>Rx</sub>. Under the terms of the agreement, we received an upfront payment of $30 million in April&#160;2013.&#160;In December 2016, we updated development activities for IONIS-HTT<sub>Rx</sub> and as a result we were eligible for an additional $3 million payment, which we achieved in 2017. We are eligible to receive up to $365 million in a license fee and milestone payments including up to $70 million for the achievement of development milestones, up to $170 million for the achievement of regulatory milestones and up to $80 million for the achievement of commercialization milestones. In addition, we are eligible to receive up to $136.5 million in milestone payments for each additional drug successfully developed.&#160;We are also eligible to receive tiered royalties up to the mid-teens on any sales of any product resulting from this alliance. From inception through September 2018, we have received over $110 million in upfront fees, milestone payments and license fees for advancing IONIS-HTT<sub>Rx</sub>, including the $45 million license fee we received in January 2018 for IONIS-HTT<sub>Rx</sub>. We will achieve the next payment of $35 million if Roche initiates a pivotal study for IONIS-HTT<sub>Rx</sub>.</div><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for Roche. We determined the transaction price to be the $30 million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. 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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 are exploring the drug in a severe and rare renal indication.&#160;</font>Roche<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#160;has the option to license IONIS-FB-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#160;at the completion of these studies. 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We did not have any deferred revenue from our relationship with GSK at September 30, 2018 or December 31, 2017.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Akcea Collaborations</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The following collaboration agreements relate to Akcea, our majority owned affiliate. Our consolidated results include all the revenue earned and cash received under these collaboration agreements. 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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Novartis</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In January 2017, we and Akcea initiated a collaboration with Novartis to develop and commercialize AKCEA-APO(a)-L<sub>Rx</sub> and AKCEA-APOCIII-L<sub>Rx</sub>.<sub>&#160;</sub>Under the collaboration agreement, Novartis has an exclusive option to further develop and commercialize AKCEA-APO(a)-L<sub>Rx</sub> and AKCEA-APOCIII-L<sub>Rx</sub>. 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 drug. If Novartis exercises an option for one of these drugs, Novartis will be responsible for all further global development, regulatory and co-commercialization activities and costs for such drug.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">Akcea received a $75 million upfront payment in the first quarter of 2017, of which it retained $60 million and paid us $15 million as a sublicense fee. If Novartis exercises its option for a drug, Novartis will pay Akcea a license fee equal to $150 million for each drug it licenses. In addition, for AKCEA-APO(a)-L<sub>Rx</sub>, Akcea is eligible to receive up to $600 million in milestone payments, including $25 million for the achievement of a development milestone, up to $290 million for the achievement of regulatory milestones and up to $285 million for the achievement of commercialization milestones. In addition, for AKCEA-APOCIII-L<sub>Rx</sub>, Akcea is eligible to receive up to $530 million in milestone payments, including $25 million for the achievement of a development milestone, up to $240 million for the achievement of regulatory milestones and up to $265 million for the achievement of commercialization milestones. Akcea is also eligible to receive tiered royalties in the mid-teens to low 20 percent range on net sales of AKCEA-APO(a)-L<sub>Rx</sub> and AKCEA-APOCIII-L<sub>Rx</sub>. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Novartis will reduce these royalties upon the expiration of certain patents or if a generic competitor negatively impacts the product in a specific country. </font>Akcea will pay 50 percent of these license fees, milestone payments and royalties to us as a sublicense fee.<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> Akcea plans to co-commercialize any licensed drug commercialized by Novartis in selected markets under terms and conditions that we plan to negotiate with Novartis in the future, through its specialized sales force.</font></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In conjunction with this collaboration, we and Akcea entered into a SPA with Novartis. As part of the SPA, Novartis purchased 1.6 million shares of our common stock for $100 million in the first quarter of 2017. As part of the SPA, Novartis was required to purchase $50 million of Akcea&#8217;s common stock at the IPO price or our common stock at a premium if an IPO did not occur by April 2018. Under the SPA, in July 2017, Novartis purchased $50 million of Akcea&#8217;s common stock in a separate private placement concurrent with the completion of its IPO at a price per share equal to the IPO price.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">At the commencement of this collaboration, we identified four separate performance obligations:</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">R&amp;D services for AKCEA-APO(a)-L<sub>Rx</sub>;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">R&amp;D services for AKCEA-APOCIII-L<sub>Rx</sub>;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">API for AKCEA-APO(a)-L<sub>Rx</sub>; and</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">API for AKCEA-APOCIII-L<sub>Rx</sub>.</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We determined that the R&amp;D services for each drug and the API for each drug were distinct from our other performance obligations.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">We are recognizing revenue related to the R&amp;D services for the AKCEA-APO(a)-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> and AKCEA-APOCIII-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> performance obligations as we perform services </font>based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">. </font>We<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> currently estimate we will satisfy the significant portion of our performance obligation for AKCEA-APO(a)-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; 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We recognized the amount attributed to the API supply for AKCEA-APO(a)-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> when we delivered it to Novartis in 2017. We recognized the amount attributed to the API supply for AKCEA-APOCIII-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> when we delivered it to Novartis in May 2018.</font></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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. 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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_SegmentReportingDisclosureTextBlock', window );">Segment Information and Concentration of Business Risk</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;">7.&#160; Segment Information and Concentration of Business Risk</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">We have two reportable segments Ionis Core and Akcea Therapeutics. </font>At September 30, 2018 we owned approximately 75 percent of Akcea.<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#160;</font>In October 2018, we received an additional 1.7 million shares of Akcea&#8217;s stock when TEGSEDI was approved by the FDA, increasing our ownership percentage to 76 percent. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Segment income (loss) from operations includes revenue less operating expenses attributable to each segment.</font></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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 drugs for us and our partners. 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font-family: 'Times New Roman', Times, serif; color: #000000;">12,000</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(7,200</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; 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border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">145,395</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 10pt; text-indent: -10pt;">Total operating expenses</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; 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text-align: center;">Akcea Therapeutics</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Elimination of</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Intercompany Activity</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(72,157</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr></table><div><br /></div><table cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">37,247</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td></tr></table><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The following table shows our total assets by segment at September 30, 2018 and December 31, 2017 (in thousands), respectively.</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"><tr><td valign="bottom" style="width: 42%; 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font-family: 'Times New Roman', Times, serif; color: #000000;">2,446,425</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">379,128</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; 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font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We have historically funded our operations from collaborations with corporate partners and a relatively small number of partners have accounted for a significant percentage of our revenue. 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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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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Basis of Presentation (Policies)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<tr><th class="th"><div>Sep. 30, 2018</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="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended September 30, 2018 and 2017 on the same basis as the audited financial statements for the year ended December 31, 2017. 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, 2017 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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, which we formed in December 2014. </font>Prior to Akcea&#8217;s <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">initial public offering, or IPO,</font> 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 <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">68 percent </font>of Akcea. In the second and third 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. We reflected the increase in our ownership in these financial statements. In October 2018, we received an additional 1.7 million shares of Akcea&#8217;s stock when TEGSEDI received marketing authorization in the U.S., increasing our ownership to approximately 76 percent. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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; color: #000000; font-style: italic;">Significant Accounting Policies,</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> 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 for basis of accounting, or basis of presentation, used to prepare the financial statements (for example, US Generally Accepted Accounting Principles, Other Comprehensive Basis of Accounting, IFRS).</p></div>
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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;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6850086080">
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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">9 Months Ended</th>
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<tr><th class="th"><div>Sep. 30, 2018</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>
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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 );">Revenue Recognition</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Revenue Recognition</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><u>Adoption of New Revenue Recognition Accounting Standard (Topic 606)</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">In May 2014, the FASB issued accounting guidance on the recognition of revenue from customers. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">This guidance supersedes the revenue recognition requirements we previously followed in Accounting Standards Codification, or ASC, Topic 605, </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;">Revenue Recognition</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">, or Topic 605, and created a new Topic 606, </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;">Revenue from Contracts with Customers</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">, or Topic 606. </font>Under Topic 606, an entity will recognize revenue when it transfers control of promised goods or services to customers in an amount that reflects what the entity expects to receive in exchange for the goods or services. Further, an entity will recognize revenue upon satisfying the performance obligation(s) under the related contract. We adopted Topic 606 on January 1, 2018 under the full retrospective approach, which required us to revise our prior period revenue. Under Topic 606, we were required to review all of our ongoing collaboration agreements in which we recognized revenue after January 1, 2016. We were required to assess what our revenue would have been for the period from January 1, 2016 to December 31, 2017 under Topic 606. As a result of this analysis, we determined that the cumulative revenue we would have recognized under Topic 606 decreased by $53.6 million. We recorded this amount as a cumulative adjustment to our accumulated deficit as of December 31, 2017. 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border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">At December 31, 2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#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;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">As Previously</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Reported under</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; 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font-family: 'Times New Roman', Times, serif; color: #000000;">11,312</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Net income (loss)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; 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The change in our revenue was primarily due to:</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>A change in how we recognize milestone payments:</u></font> Topic 606 requires us to amortize more of the milestone payments we achieve, rather than recognizing the milestone payments in full in the period in which we achieved the milestone event as we did under Topic 605. This change resulted in an increase of $0.5 million and $27.9 million for the three and nine months ended September 30, 2017, respectively.</div></td></tr></table></div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><u>A change in how we calculate revenue for payments we are recognizing into revenue over time:</u></font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Under Topic 605, we amortized payments into revenue evenly over the period of our obligations. When we made a change to our estimated completion period, we recognized that change on a prospective basis. Under Topic 606, we are required to use an input method to determine the amount we amortize each reporting period. Each period, we review our &#8220;inputs&#8221; such as our level of effort expended, including the time we estimate it will take us to complete the activities, or costs incurred relative to the total expected inputs to satisfy the performance obligation. For certain collaborations, such as Bayer, Janssen and Novartis, the input method resulted in a change to the revenue we had previously recognized using a straight-line amortization method.</font><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;">This change resulted in a decrease of $4.0 million and $17.5 million for the three and nine months ended September 30, 2017, respectively.</font></div></td></tr></table></div><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">Our updated revenue recognition policy reflecting Topic 606 is as follows:</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"><u>Our Revenue Sources</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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 condensed consolidated balance sheet.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We expect to add product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 as a result of TEGSEDI&#8217;s approval in the U.S., EU and Canada. We will also recognize as commercial revenue future sales milestone payments and royalties we earn under our partnerships.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Research and development revenue under collaborative agreements</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">Our collaboration agreements are detailed in Note 6, <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements.</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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;"><u>Steps to Recognize Revenue</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We use a five step process to determine the amount of revenue we should recognize and when we should recognize it. The five step process is as follows:</div><div><br /></div><div style="text-align: left;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;">1.</td><td style="width: auto; vertical-align: top; text-align: left;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;">Identify the contract</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; text-indent: 36pt;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</div><div><br /></div><div style="text-align: left;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: left;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">We and our partner approved the contract and we are both committed to perform our obligations;</div></td></tr></table></div><div style="text-align: left;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: left;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">We have identified our rights, our partner&#8217;s rights and the payment terms;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and</div></td></tr></table></div><div style="text-align: left;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: left;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">We believe collectability is probable.</div></td></tr></table></div><div><br /></div><div style="text-align: left;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;">2.</td><td style="width: auto; vertical-align: top; text-align: left;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;">Identify the performance obligations</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">Often times when we enter into a collaboration agreement in which we provide our partner with an option to license a drug 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 drug 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 drug or requests additional goods or services, then we identify a new performance obligation for that item.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;">3.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;">Determine the transaction price</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.</div><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;">4.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;">Allocate the transaction price</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Estimated future product sales;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Estimated royalties on future product sales;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Contractual milestone payments;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Expenses we expect to incur;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Income taxes; and</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">A discount rate.</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We typically estimate the selling price of R&amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;D services include:</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">The number of internal hours we estimate we will spend performing these services;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">The estimated cost of work we will perform;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">The estimated cost of work that we will contract with third parties to perform; and</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">The estimated cost of API we will use.</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">For purposes of determining the stand-alone selling price of the R&amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; font-weight: bold; color: #000000; font-style: italic; align: right;">5.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; font-style: italic;">Recognize revenue</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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; color: #000000;">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></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; text-indent: 36pt;">The following are examples of when we typically recognize revenue based on the types of payments we receive.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: left; text-indent: 36pt;"><u>Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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. Our accounting for SPINRAZA royalties did not change as a result of adopting Topic 606.</div><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: left; text-indent: 36pt;"><u>Research and development revenue under collaboration agreements:</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: left; text-indent: 36pt;"><u>Upfront Payments</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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 new SMA collaboration with Biogen, we received a $25 million upfront payment in December 2017. We allocated the upfront payment to our single performance obligation, R&amp;D services. We are amortizing the $25 million upfront payment using an input method over the estimated period of time we are providing R&amp;D services. Refer to <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Note 6, </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;">Collaborative Arrangements and Licensing Agreements</font>, for further discussion. Under Topic 605, we amortized upfront payments evenly over the period of our obligation.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: justify; text-indent: 36pt;"><u>Milestone Payments</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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 drug is approved by the applicable regulator. We will recognize sales based milestone payments in the period we achieve the milestone under the sales-based royalty exception allowed under accounting rules.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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. Under Topic 606, we allocated this payment to our R&amp;D services performance obligation. We are recognizing revenue from this milestone payment over our estimated period of performance. Under Topic 605, this milestone payment was recognized in full in the third quarter of 2017, which was the period in which we achieved the milestone event.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the milestone event. For example, in the third quarter of 2018, we earned a $10 million milestone payment when AstraZeneca initiated a Phase 1 study of IONIS-AZ4-2.5-L<sub>Rx</sub>. Our revenue recognition of milestone payments we earn based on our partners&#8217; activities did not change as a result of adopting Topic 606.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic; text-align: justify; text-indent: 36pt;"><u>License Fees</u></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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 third quarter of 2018, we earned a $12 million license fee when our majority-owned affiliate, Akcea, <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">entered into an exclusive license agreement with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America</font>. Our recognition of license fees did not change as a result of adopting Topic 606.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;">Amendments to Agreements</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">1)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">2)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">If the goods and/or services are at a stand-alone selling price.</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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 standalone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> 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="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> 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="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> and to initiate development of IONIS-FXI-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">, 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="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> and IONIS-FXI-L</font><sub style="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">. 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="color: #000000;">Rx</sub><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">, 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; color: #000000;">Note 6, </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;">Collaborative Arrangements and Licensing Agreements</font>, for further discussion <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">of our accounting treatment for our Bayer collaboration. </font>Our allocation of the consideration we received for the Bayer amendment did not change as a result of adopting Topic 606. However, the method in which we are recognizing revenue related to our R&amp;D services performance obligation did change. We are amortizing revenue related to our R&amp;D services performance obligation using the input method under Topic 606.</div><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;">Multiple Agreements</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Whether the agreements were negotiated together with a single objective;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Whether the goods and/or services promised under the agreements are a single performance obligation.</div></td></tr></table></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify;">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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; color: #000000;">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. Refer to Note 6, </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic;">Collaborative Arrangements and Licensing Agreements</font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;"> for further discussion of the accounting treatment for the 2018 strategic neurology collaboration with Biogen.</font></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left; margin-left: 54pt; text-indent: -18pt;">Contracts Receivable</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Our contracts receivable balance represents the amounts we have billed our partners for goods we have delivered or services we have performed that are due to us unconditionally. When we bill our partners 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</font>. Our contracts receivable balance as of December 31, 2017 did not change when we adopted Topic 606.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; margin-left: 54pt; text-indent: -18pt;">Unbilled SPINRAZA Royalties</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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>Our unbilled SPINRAZA royalties as of December 31, 2017 did not change when we adopted Topic 606.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left; margin-left: 54pt; text-indent: -18pt;">Deferred Revenue</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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 and nine months ended September 30, 2018, we recognized $37.2 million and $80.4 million of revenue from amounts that were in our beginning deferred revenue balances for those periods, respectively. During the three and nine months ended September 30, 2017, we recognized $31.6 million and $84.4 million of revenue from amounts that were in our beginning deferred revenue balances for those periods, respectively. 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text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">As Previously</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Reported under</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Topic 605</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Topic 606</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Adjustment</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">As Revised</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">Current portion of deferred revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; 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color: #000000;">18,871</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">125,336</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">35,318</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">108,026</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; 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vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">54,189</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">233,362</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td></tr></table><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">Our deferred revenue balance increased $54.2 million at December 31, 2017 under Topic 606, compared to Topic 605. The increase was primarily related to the change in the accounting for certain milestone payments and the way in which we amortize payments. Under Topic 605, we previously recognized the majority of the milestone payments we earned in the period we achieved the milestone event, which did not impact our deferred revenue balance. Under Topic 606 we are now amortizing more milestone payments over the period of our performance obligation, which adds to our deferred revenue balance. Additionally, under Topic 605 we amortized payments evenly over the period of our obligation. Under Topic 606, we are required to use an input method to determine the amount we amortize each reporting period. The increase in deferred revenue relates to agreements with the following partners:</div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$24.2 million from Biogen;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$15.9 million from AstraZeneca;</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$11.8 from Novartis; and</div></td></tr></table></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 36pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">&#9679;</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$2.3 million from other partners.</div></td></tr></table></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><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Noncontrolling Interest in Akcea Therapeutics, Inc.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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; color: #000000;">&#160;</font>of Akcea. In the second and third 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. We reflected this increase in our ownership percentage in these financial statements as an adjustment to noncontrolling interest. In October 2018, we received an additional 1.7 million shares of Akcea&#8217;s stock when TEGSEDI received marketing authorization in the U.S., increasing our ownership to approximately 76 percent. <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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 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></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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Cash, cash equivalents and investments</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At September 30, 2018, we held an equity investment in one publicly held company, 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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In January 2018, we adopted the amended accounting guidance related to the recognition, measurement, presentation, and disclosure of certain financial instruments. The amended guidance requires us to measure and record our equity investments at fair value. Additionally, the amended accounting guidance requires us to recognize the changes in fair value in our consolidated statement of operations, instead of through accumulated other comprehensive income. Prior to 2018, we accounted for our equity investments in privately held companies under the cost method of accounting. Under the amended guidance we account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. Our adoption of this guidance did not have an impact on our results.</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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Inventory valuation</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">We reflect our inventory on our 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 drugs because until we use these raw materials they have alternative future uses. We include in inventory raw material costs for drugs 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 drug. For example, if one of our drugs failed, we could use the raw materials for that drug to manufacture our other drugs. We expense these costs as R&amp;D expenses when we begin to manufacture API for a particular drug if the drug has not been approved for marketing by a regulatory agency.</div><div style="text-align: justify;"><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">We obtained the first regulatory approval for TEGSEDI in July 2018. At September 30, 2018 and December 31, 2017, 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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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 drugs and historical write-offs. We did not record any inventory write-offs for the nine months ended September 30, 2018 and 2017.</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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; margin-left: 36pt;">Research, development and patent expenses</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">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><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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_IntangibleAssetsFiniteLivedPolicy', window );">Patent Expenses</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock', window );">Long-Lived Assets</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Long-lived assets</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We evaluate long-lived assets, which include property, plant and equipment 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.</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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Use of estimates</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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.</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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Basic and diluted net income (loss) per share</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">Basic net income (loss) per share</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The calculation of total net income (loss) attributable to our common stockholders for the three and nine months ended September 30, 2018 and 2017 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. As a result of this calculation, our&#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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">Our basic net loss per share for the three months ended <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">September 30, 2018</font>, was calculated as follows (in thousands, except per share amounts):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;">Three months ended September 30, 2018</div></td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Weighted</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Average Shares</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Owned in Akcea</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Akcea&#8217;s</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Net Income (Loss)</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Per Share</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Ionis&#8217; Portion of</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Akcea&#8217;s Net Loss</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: top;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Common shares</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">65,538</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(0.73</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(47,843</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Akcea&#8217;s net loss attributable to our ownership</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(47,843</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Ionis&#8217; stand-alone net income</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; 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vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(110,680</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Ionis&#8217; stand-alone net income</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; 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background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(43,162</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Weighted average shares outstanding</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">132,518</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Basic net loss per share</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; 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font-weight: bold; color: #000000; text-align: left;">Three months ended September 30, 2017</div></td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Weighted</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Average Shares</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Owned in Akcea</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; 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font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(0.33</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(12,063</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Preferred shares</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">5,651</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; 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vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(57</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Akcea&#8217;s net loss attributable to our ownership</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(12,120</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Ionis&#8217; stand-alone net income</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">10,144</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Net loss available to Ionis common stockholders</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; 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margin-left: 9.1pt; text-indent: -9.1pt;">Weighted average shares outstanding</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">124,370</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Basic net income per share</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(0.02</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; 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color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(38,435</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; 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font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Akcea&#8217;s net loss attributable to our ownership</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(83,914</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Ionis&#8217; stand-alone net income</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; 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border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">24</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; 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color: #000000;">16,321</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">125,858</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0.13</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td></tr></table><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">For the nine months ended September 30, 2017, the calculation excluded the 1 percent and 2&#190; percent notes because the effect on diluted earnings per share was anti-dilutive.</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_StockholdersEquityPolicyTextBlock', window );">Accumulated Other Comprehensive Loss</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Accumulated other comprehensive loss</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We include unrealized gains and losses on investments, net of taxes, in accumulated other comprehensive income (loss) along with&#160;adjustments we make to reclassify realized gains and losses on investments from other accumulated comprehensive income (loss) to our condensed consolidated statement of operations. 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padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Nine Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">&#160;</div></td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Beginning balance accumulated other comprehensive loss</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; 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text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; 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text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">159</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Ending balance accumulated other comprehensive loss</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; 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vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(30,199</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(32,532</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(30,199</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr></table><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 18pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">(1)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">There was no income tax expense or benefit related to elements of other comprehensive income (loss) for the three and nine months ended September 30, 2018 and 2017.</div></td></tr></table></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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Convertible debt</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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.</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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Segment information</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">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 drugs to treat patients with rare and serious diseases<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">. 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></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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: justify; text-indent: 36pt;">Stock-based compensation expense</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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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font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">2.3%</div></td><td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">1.8%</div></td></tr><tr><td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Dividend yield</div></td><td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">0.0%</div></td><td style="width: 2.66%; 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vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">63,642</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td></tr></table><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">As of September 30, 2018, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options and RSUs was $139.5 million and $32.6 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 1.3 years and 1.6 years, respectively.</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_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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left; text-indent: 36pt;">Impact of recently issued accounting standards</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In February 2016, the FASB issued amended accounting guidance related to lease accounting, which will require us to record all leases with a term longer than one year on our balance sheet. When we record leases on our balance sheet under the new guidance, we will record a liability with a value equal to the present value of payments we will make over the life of the lease and an asset representing the underlying leased asset. The new accounting guidance requires us to determine if our leases are operating or financing leases. We will record expense for operating leases on a straight-line basis as an operating expense. If we determine a lease is a financing&#160;lease, we will record both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. The new lease standard is effective for annual and interim periods beginning after December 15, 2018, with early adoption permitted. We will adopt this guidance on January 1, 2019. We can choose from two methods of adoption. The first method requires us to reflect our leases on our balance sheet in the earliest comparative period presented in our financial statements. The second method requires us to reflect the impact of adoption on the date we adopt the new guidance and recognize a cumulative-effect adjustment to the opening balance of our accumulated deficit in that period. We are currently determining the method we will use to adopt the new guidance and assessing the effects the new guidance will have on our consolidated financial statements and disclosures.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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 consolidated financial statements and disclosures.</div><div><br /></div><div style="text-align: left;"><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In December 2017, the SEC staff issued guidance to address how companies should account for the Tax Act of 2017, or the Tax Act, when an entity does not have the necessary information to complete the accounting for the Tax Act and gives entities up to one year from the enactment of the Tax Act to finalize their amounts. We recognized provisional amounts in our 2017 financial statements and in these financial statements. The ultimate impact may differ materially from these provisional amounts due to, among other things, additional analysis, changes in our interpretations and assumptions, additional regulatory guidance that may be issued, and other actions we may take resulting from the Tax Act. We will assess and update our provisional amounts and disclosures, as necessary, at year end 2018.</div><div style="text-align: justify; text-indent: 36pt;"><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In February 2018, the FASB issued updated guidance for reclassification of tax effects from accumulated other comprehensive income (loss). The updated guidance gives entities an option to reclassify amounts included in accumulated other comprehensive income (loss) that under the Tax Act do not have a way to be relieved, and allows a one-time reclassification to retained earnings. The updated guidance is effective for all entities for fiscal years beginning after December 31, 2018, and interim periods within those fiscal years. Early adoption is permitted, and adoption is optional. We are currently assessing the effects this updated guidance could have on our consolidated financial statements and timing of potential adoption.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">In June 2018, the FASB issued updated guidance to simplify the accounting for stock-based compensation expense for nonemployees. Specifically, we are now expensing grants to nonemployees in a similar manner as grants to employees and our Board of Directors. Previously, we had to re-value these grants at each reporting period to reflect the current fair value. Under the amended guidance, we value grants to nonemployees when we grant them and we will not adjust their value for future changes. We adopted this guidance in the second quarter of 2018 on a prospective basis. The updated guidance did not have a material impact to our financial results.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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 consolidated financial statements and timing of adoption.</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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 anticipate we will adopt this updated guidance on January 1, 2019 and we do not expect it to have a significant impact on our disclosures.</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>
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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 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>
<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 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>
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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>
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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>
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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>
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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 its capital stock transactions, including dividends and accumulated other comprehensive income.</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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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies (Tables)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfNewAccountingPronouncementsAndChangesInAccountingPrinciplesTextBlock', window );">Adjustments Made to Adopt New Revenue Accounting Guidance</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The following tables summarize the adjustments we were required to make to amounts we originally reported in 2017 to adopt Topic 606 (in thousands, except per share amounts):</div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;">Condensed Consolidated Balance Sheet</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">At December 31, 2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#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;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">As Previously</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Reported under</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; 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font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -9pt;">Total revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">120,911</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; 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vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;">SPINRAZA royalties</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">60,467</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">60,467</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 8.85pt;">Licensing and other royalty revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">4,983</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">656</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">5,639</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: 17.75pt;">Total commercial revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">65,450</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">656</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">66,106</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;">Research and development revenue under collaborative agreements</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">269,917</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">10,364</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">280,281</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -9pt;">Total revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">335,367</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">11,020</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">346,387</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Income from operations</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">26,227</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">11,020</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">37,247</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Net income (loss)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(12,636</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">11,020</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(1,616</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: left; margin-left: 9pt; text-indent: -9pt;">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(8,716</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">11,982</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">3,266</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Net income (loss) per share, basic</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0.02</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0.11</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0.13</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Net income (loss) per share, diluted</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0.02</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0.11</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0.13</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr></table><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic; text-align: justify; text-indent: 36pt;">Condensed Consolidated Statement of Cash Flows</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td valign="bottom" style="vertical-align: bottom; 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color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">31,071</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">Cash and cash equivalents at beginning of period</div></td><td valign="bottom" style="width: 1%; 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vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">159,184</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr></table><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The following table summarizes the adjustments we were required to make to our deferred revenue amounts to adopt Topic 606 (in thousands):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="11" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">At December 31, 2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">As Previously</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Reported under</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Topic 605</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Topic 606</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Adjustment</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">As Revised</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">Current portion of deferred revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">106,465</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">18,871</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">125,336</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">Long-term portion of deferred revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">72,708</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">35,318</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">108,026</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt;">Total deferred revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">179,173</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">54,189</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">233,362</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#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_us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock', window );">Basic Net Loss per Share</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; text-align: justify; text-indent: 36pt;">Our basic net loss per share for the three months ended <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">September 30, 2018</font>, was calculated as follows (in thousands, except per share amounts):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;">Three months ended September 30, 2018</div></td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Weighted</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Average Shares</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Owned in Akcea</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Akcea&#8217;s</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Net Income (Loss)</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Per Share</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Ionis&#8217; Portion of</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Akcea&#8217;s Net Loss</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: top;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Common shares</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">65,538</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(0.73</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(47,843</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Akcea&#8217;s net loss attributable to our ownership</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(47,843</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Ionis&#8217; stand-alone net income</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">43,226</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Net loss available to Ionis common stockholders</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(4,616</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Weighted average shares outstanding</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 2px; text-align: right; background-color: #cceeff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">143,314</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9.1pt; text-indent: -9.1pt;">Basic net loss per share</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #ffffff;">&#160;</td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(0.03</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr></table><div><br /></div></div><span></span>
</td>
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<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">For the nine months ended September 30, 2017, 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 those periods. Diluted common equivalent shares for the nine months ended September 30, 2017 consisted of the following (in thousands except per share amounts):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: left;">Nine months ended September 30, 2017</div></td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Income</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">(Numerator)</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Shares</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">(Denominator)</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Per-Share</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Amount</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: top;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; padding-bottom: 4px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Net income available to Ionis common stockholders</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">16,321</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; padding-bottom: 4px; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">123,746</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0.13</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: top; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Effect of dilutive securities:</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; 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color: #000000;">16,321</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">125,858</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0.13</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td></tr></table><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">For the nine months ended September 30, 2017, the calculation excluded the 1 percent and 2&#190; percent notes because the effect on diluted earnings per share was anti-dilutive.</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_ScheduleOfAccumulatedOtherComprehensiveIncomeLossTableTextBlock', window );">Changes in Accumulated Other Comprehensive Income (Loss)</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">We include unrealized gains and losses on investments, net of taxes, in accumulated other comprehensive income (loss) along with&#160;adjustments we make to reclassify realized gains and losses on investments from other accumulated comprehensive income (loss) to our condensed consolidated statement of operations. 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vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(30,199</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(32,532</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(30,199</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; 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</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_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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">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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font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">2.3%</div></td><td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">1.8%</div></td></tr><tr><td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Dividend yield</div></td><td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">0.0%</div></td><td style="width: 2.66%; 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vertical-align: bottom; background-color: #cceeff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">66.1%</div></td></tr><tr><td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Expected life</div></td><td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">4.6 years</div></td><td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">4.5 years</div></td></tr></table><div><br /></div><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: left; text-indent: 36pt;">Board of Director Stock Options:</div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 60%; border-collapse: collapse;"><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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Nine Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td></tr><tr><td style="width: 70.68%; vertical-align: bottom;">&#160;</td><td colspan="2" style="width: 13.37%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td style="width: 2.66%; vertical-align: bottom;">&#160;</td><td colspan="2" style="width: 13.3%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td></tr><tr><td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Risk-free interest rate</div></td><td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">2.8 %</div></td><td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">2.2 %</div></td></tr><tr><td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Dividend yield</div></td><td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">0.0 %</div></td><td style="width: 2.66%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td style="width: 2.65%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">0.0 %</div></td></tr><tr><td style="width: 70.68%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Volatility</div></td><td style="width: 2.71%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">61.5 %</div></td><td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">61.2 %</div></td></tr><tr><td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Expected life</div></td><td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">6.6 years</div></td><td style="width: 2.66%; 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</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_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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; font-style: italic; text-align: justify; text-indent: 36pt;">ESPP:</div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 60%; border-collapse: collapse;"><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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Nine Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td></tr><tr><td style="width: 70.68%; vertical-align: bottom;">&#160;</td><td colspan="2" style="width: 13.37%; 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color: #000000; text-align: right;">1.8%</div></td><td style="width: 2.66%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td style="width: 2.65%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">0.8%</div></td></tr><tr><td style="width: 70.68%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Dividend yield</div></td><td style="width: 2.71%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td style="width: 10.66%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">0.0%</div></td><td style="width: 2.66%; 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vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: right;">6 months</div></td></tr></table><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_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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The following table summarizes stock-based compensation expense for the three and nine months ended September 30, 2018 and 2017 (in thousands). 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padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Nine Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; 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vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">16,181</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">57,698</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">48,443</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Selling, general and administrative</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">16,103</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">5,291</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">39,512</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">15,199</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; 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text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">21,472</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">97,210</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; 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vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 18pt; text-indent: -9pt;">Debt securities issued by the U.S. Treasury</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">9,872</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; 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text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Corporate debt securities</div></td><td valign="bottom" style="width: 1%; 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color: #000000;">911,594</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">14</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(3,072</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">908,536</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td></tr></table><div><br /></div><div style="text-align: left;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 18pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">(1)</td><td style="width: auto; 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</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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The following is a summary of our investments we consider to be temporarily impaired at September 30, 2018. 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-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Temporary Impairment</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">More than 12 Months of</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Temporary Impairment</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="6" valign="bottom" style="vertical-align: bottom; 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vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">164,053</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(99</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 30%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td><td valign="bottom" style="width: 7px; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">48</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; 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vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(690</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: right; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 7%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">77,434</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; 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<th class="th" colspan="1">9 Months Ended</th>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The following tables present the major security types we held at September 30, 2018 and December 31, 2017 that are regularly measured and carried at fair value. At September 30, 2018 and December 31, 2017, we did not have any financial instruments that we valued using Level 3 inputs. 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font-family: 'Times New Roman', Times, serif; color: #000000;">1,334,785</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td></tr></table><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 80%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">At</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">December 31, 2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; 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vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Corporate debt securities (3)</div></td><td valign="bottom" style="width: 1%; 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vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">647,461</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Debt securities issued by U.S. government agencies (3)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">136,325</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">136,325</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Debt securities issued by the U.S. Treasury (3)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">30,818</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">30,818</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 64%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (4)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">93,932</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">93,932</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr style="height: 16px;"><td valign="bottom" style="width: 64%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Total</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">994,798</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">117,080</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">877,718</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;">&#160;</td></tr></table><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 18pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">(1)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Included in cash and cash equivalents on our condensed consolidated balance sheet.</div></td></tr></table></div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 18pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">(2)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">At September 30, 2018, $19.7 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.</div></td></tr></table></div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 18pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">(3)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">Included in short-term investments on our condensed consolidated balance sheet.</div></td></tr></table></div><div><br /></div><div style="text-align: justify;"><table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 100%;"><tr><td style="width: 18pt;"></td><td style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 18pt; vertical-align: top; color: #000000; align: right;">(4)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">At December 31, 2017, $3.5 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.</div></td></tr></table></div><div><br /></div></div><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_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationTextBlock', window );">Reconciliation of Assets Measured at Fair Value on a Recurring Basis Using Significant Unobservable Inputs (Level 3)</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The following is a reconciliation of the potential premium we would have received if Akcea had not completed its IPO, measured at fair value on a recurring basis using significant unobservable inputs (Level 3) for the nine months ended September 30, 2017 (in thousands):</div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"><tr><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 88%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; margin-left: 9pt; text-indent: -9pt;">Beginning balance of Level 3 instruments at January 1, 2017</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">&#8212;</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 88%; vertical-align: bottom; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; margin-left: 9pt; text-indent: -9pt;">Value of the potential premium we would have received from Novartis at inception of the SPA (January 2017)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">5,035</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 88%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; margin-left: 9pt; text-indent: -9pt;">Recurring fair value adjustment during the nine months ended September 30, 2017</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(5,035</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td></tr><tr><td valign="bottom" style="width: 88%; 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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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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements (Tables)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2018</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_CollaborativeArrangementsAndLicensingAgreementsAstraZenecaMember', window );">AstraZeneca [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_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', 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_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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with AstraZeneca (in millions, except percentage amounts):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">&#160;</div></td><td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Three Months Ended</div><div style="font-size: 10pt; 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vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">14.8</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Percentage of total revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; 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vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">4</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">21</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">4</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td></tr></table><div><br /></div></div><span></span>
</td>
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<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_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></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_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">During the three and nine months ended September 30, 2018 and 2017, 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">&#160;</div></td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Three Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Nine Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">&#160;</div></td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;">SPINRAZA royalties (commercial revenue)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">70.0</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">32.9</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">167.7</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">60.5</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">R&amp;D revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">34.8</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">54.9</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">66.9</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">137.1</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -9pt;">Total revenue from our relationship with Biogen</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">104.8</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">87.8</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">234.6</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">197.6</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -9pt;">Percentage of total revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">72</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">74</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">58</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">57</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</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_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember', window );">Bayer [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_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [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_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Bayer (in millions, except percentage amounts):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">&#160;</div></td><td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Three Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Nine Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">&#160;</div></td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;">R&amp;D revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">1.9</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0.4</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">3.3</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">66.0</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Percentage of total revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">1</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">1</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">19</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</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_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember', window );">Janssen Biotech, Inc. [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_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></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_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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Janssen (in millions, except percentage amounts):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">&#160;</div></td><td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Three Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Nine Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">&#160;</div></td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;">R&amp;D revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0.9</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">3.4</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">6.6</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">18.1</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Percentage of total revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">1</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">3</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">2</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">5</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</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_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member]</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_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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">During the three and nine months ended September 30, 2018 and 2017, 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">&#160;</div></td><td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Three Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Nine Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">&#160;</div></td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;">R&amp;D revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">7.2</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">9.9</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">42.7</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">21.7</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Percentage of total revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">5</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">8</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">10</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">6</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">During the three and nine months ended September 30, 2018 and 2017, 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="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">&#160;</div></td><td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Three Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Nine Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">&#160;</div></td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;">R&amp;D revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">1.8</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">4.5</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">5.4</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">5.9</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Percentage of total revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">1</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">4</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">1</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">2</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember', window );">GSK [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><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">&#160;</div></td><td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Three Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="7" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Nine Months Ended</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">September 30,</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left;">&#160;</div></td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2018</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td colspan="3" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">2017</div></td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 27pt; text-indent: -27pt;">R&amp;D revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0.1</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">4.6</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">1.5</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">14.4</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Percentage of total revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">4</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">%</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; 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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_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember', window );">PTC Therapeutics [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
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<tr class="ro">
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vertical-align: bottom; border-bottom: #000000 2px solid; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 2px solid; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">0.0</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left; background-color: #cceeff;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: bottom; padding-bottom: 2px; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 9pt; text-indent: -9pt;">Percentage of total revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; 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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6829933568">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Segment Information and Concentration of Business Risk (Tables)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;">Total segment revenue</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">178,061</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; 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text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: top;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;">Commercial revenue:</div></td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="width: 52%; vertical-align: top; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 25.2pt;">SPINRAZA royalties</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; 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text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; text-align: left;">&#160;</td></tr><tr><td valign="bottom" style="vertical-align: top;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: left; margin-left: 7.2pt;">Commercial revenue:</div></td><td valign="bottom" style="vertical-align: bottom;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td><td nowrap="nowrap" valign="bottom" style="vertical-align: bottom; 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font-family: 'Times New Roman', Times, serif; color: #000000;">(54,497</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #ffffff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #ffffff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">309,140</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; 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font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 9%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">37,247</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td></tr></table><div><br /></div><div><br /></div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000; text-align: justify; text-indent: 36pt;">The following table shows our total assets by segment at September 30, 2018 and December 31, 2017 (in thousands), respectively.</div><div><br /></div><table align="center" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; width: 70%;"><tr><td valign="bottom" style="width: 42%; 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vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Elimination of</div><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; text-align: center;">Intercompany Activity</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px; text-align: left;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 2px;">&#160;</td><td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; color: #000000; 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font-family: 'Times New Roman', Times, serif; color: #000000;">2,446,425</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">379,128</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">$</div></td><td valign="bottom" style="width: 12%; vertical-align: bottom; border-bottom: #000000 4px double; text-align: right; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">(577,641</div></td><td nowrap="nowrap" valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; text-align: left; background-color: #cceeff;"><div style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #000000;">)</div></td><td valign="bottom" style="width: 1%; vertical-align: bottom; padding-bottom: 4px; background-color: #cceeff;">&#160;</td><td valign="bottom" style="width: 1%; vertical-align: bottom; 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</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_ScheduleOfRevenueByMajorCustomersByReportingSegmentsTableTextBlock', window );">Revenue from Significant Partners</a></td>
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<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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<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_SegmentReportingAbstract</td>
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<td>duration</td>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>33
<FILENAME>R21.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;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6834909024">
<tr>
<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">1 Months Ended</th>
<th class="th" colspan="1">7 Months Ended</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>Oct. 31, 2018</div></th>
<th class="th"><div>Jul. 31, 2017</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Apr. 30, 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_ProceedsFromIssuanceOrSaleOfEquityAbstract', window );"><strong>Basis of Presentation [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_SaleOfStockPercentageOfOwnershipBeforeTransaction', window );">Percentage ownership before IPO</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="nump">68.00%<span></span>
</td>
<td class="nump">75.00%<span></span>
</td>
<td class="nump">75.00%<span></span>
</td>
<td class="nump">68.00%<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_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_ProceedsFromIssuanceOrSaleOfEquityAbstract', window );"><strong>Basis of Presentation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="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_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="nump">76.00%<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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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 when TEGSEDI received marketing authorization in the U.S. (in shares)</a></td>
<td class="nump">1.7<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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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of shares received from the subsidiary when TEGSEDI received marketing authorization in one or more countries or approval from a government agency, such as the Food and Drug Administration (FDA).</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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<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>
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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_ProceedsFromIssuanceOrSaleOfEquityAbstract</td>
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<td><strong> Data Type:</strong></td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Percentage of subsidiary's or equity investee's stock owned by parent company before stock transaction.</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 );">- 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>
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<td><strong> Data Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>34
<FILENAME>R22.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;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6853012208">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Revenue Recognition - Adoption of Topic 606 (Details) - USD ($)<br> $ / shares in Units, $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 30, 2017</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 30, 2017</div></th>
<th class="th"><div>Dec. 31, 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_StatementOfFinancialPositionAbstract', window );"><strong>Condensed Consolidated Balance Sheet [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_ContractWithCustomerLiabilityCurrent', window );">Current portion of deferred revenue</a></td>
<td class="nump">$ 157,145<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 157,145<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 125,336<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 portion of deferred revenue</a></td>
<td class="nump">523,384<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">523,384<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">108,026<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">(1,287,369)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(1,287,369)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(1,241,034)<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_MinorityInterest', window );">Noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="nump">129,594<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">129,594<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">84,267<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_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Total stockholders' equity</a></td>
<td class="nump">840,144<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">840,144<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">365,280<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_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [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="nump">145,395<span></span>
</td>
<td class="nump">$ 118,314<span></span>
</td>
<td class="nump">407,559<span></span>
</td>
<td class="nump">$ 346,387<span></span>
</td>
<td class="text">&#160;<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="num">(18,572)<span></span>
</td>
<td class="nump">11,312<span></span>
</td>
<td class="num">(72,157)<span></span>
</td>
<td class="nump">37,247<span></span>
</td>
<td class="text">&#160;<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="num">(20,365)<span></span>
</td>
<td class="num">(7,493)<span></span>
</td>
<td class="num">(87,747)<span></span>
</td>
<td class="num">(1,616)<span></span>
</td>
<td class="text">&#160;<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) attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="num">$ (4,559)<span></span>
</td>
<td class="num">$ (2,611)<span></span>
</td>
<td class="num">$ (46,335)<span></span>
</td>
<td class="nump">$ 3,266<span></span>
</td>
<td class="text">&#160;<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 );">Net income (loss) per share, basic (in dollars per share)</a></td>
<td class="num">$ (0.03)<span></span>
</td>
<td class="num">$ (0.02)<span></span>
</td>
<td class="num">$ (0.33)<span></span>
</td>
<td class="nump">$ 0.13<span></span>
</td>
<td class="text">&#160;<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 );">Net income per share, diluted (in dollars per share)</a></td>
<td class="num">$ (0.03)<span></span>
</td>
<td class="num">$ (0.02)<span></span>
</td>
<td class="num">$ (0.33)<span></span>
</td>
<td class="nump">$ 0.13<span></span>
</td>
<td class="text">&#160;<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_StatementOfCashFlowsAbstract', window );"><strong>Condensed Consolidated Statement of Cash Flows [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_ProfitLoss', window );">Net income (loss)</a></td>
<td class="num">$ (20,365)<span></span>
</td>
<td class="num">$ (7,493)<span></span>
</td>
<td class="num">$ (87,747)<span></span>
</td>
<td class="num">$ (1,616)<span></span>
</td>
<td class="text">&#160;<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_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Adjustments to reconcile net income (loss) to net cash provided by operating activities [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_IncreaseDecreaseInContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">447,168<span></span>
</td>
<td class="nump">31,071<span></span>
</td>
<td class="text">&#160;<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_CashAndCashEquivalentsAtCarryingValue', window );">Cash and cash equivalents at beginning of period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">129,630<span></span>
</td>
<td class="nump">84,685<span></span>
</td>
<td class="nump">84,685<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_CashAndCashEquivalentsAtCarryingValue', window );">Cash and cash equivalents at end of period</a></td>
<td class="nump">479,891<span></span>
</td>
<td class="nump">159,184<span></span>
</td>
<td class="nump">479,891<span></span>
</td>
<td class="nump">159,184<span></span>
</td>
<td class="nump">129,630<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_NewAccountingPronouncementOrChangeInAccountingPrincipleEffectOfChangeOnRevenueFromAmortizationOfMilestonePaymentsAchievedUnderNewRevenueGuidance', window );">Increase in revenue from amortization of milestone payments achieved under new revenue guidance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">27,900<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_NewAccountingPronouncementOrChangeInAccountingPrincipleEffectOfChangeOnRevenueFromAmortizationOfPaymentsUsingInputMethod', window );">Decrease in revenue from amortization of payments using input method under new revenue guidance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(4,000)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(17,500)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
</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_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [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="nump">82,756<span></span>
</td>
<td class="nump">34,617<span></span>
</td>
<td class="nump">181,975<span></span>
</td>
<td class="nump">66,106<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_us-gaap_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [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="nump">70,010<span></span>
</td>
<td class="nump">32,890<span></span>
</td>
<td class="nump">167,743<span></span>
</td>
<td class="nump">60,467<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>
</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_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [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="nump">12,746<span></span>
</td>
<td class="nump">1,727<span></span>
</td>
<td class="nump">14,232<span></span>
</td>
<td class="nump">5,639<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 );">Research and Development 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>
</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_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [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="nump">$ 62,639<span></span>
</td>
<td class="nump">83,697<span></span>
</td>
<td class="nump">$ 225,584<span></span>
</td>
<td class="nump">280,281<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_AccountingStandardsUpdate201409Member', window );">Topic 606 [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_us-gaap_NewAccountingPronouncementOrChangeInAccountingPrincipleRetrospectiveAdjustmentsAbstract', 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>
</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_NewAccountingPronouncementOrChangeInAccountingPrincipleCumulativeEffectOfChangeOnEquityOrNetAssets1', window );">Cumulative effect of adoption on retained earnings</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(53,600)<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_AdjustmentsForNewAccountingPronouncementsAxis=us-gaap_AccountingStandardsUpdate201409Member', window );">Topic 606 [Member] | As Previously Reported Under Topic 605 [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_us-gaap_StatementOfFinancialPositionAbstract', window );"><strong>Condensed Consolidated Balance Sheet [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_ContractWithCustomerLiabilityCurrent', window );">Current portion of deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">106,465<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_ContractWithCustomerLiabilityNoncurrent', window );">Long-term portion of deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">72,708<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_RetainedEarningsAccumulatedDeficit', window );">Accumulated deficit</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(1,187,398)<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="text">&#160;<span></span>
</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">87,847<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_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Total stockholders' equity</a></td>
<td class="text">&#160;<span></span>
</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">418,719<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_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [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">120,911<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">335,367<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="nump">13,909<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">26,227<span></span>
</td>
<td class="text">&#160;<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_ProfitLoss', window );">Net income (loss)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(4,896)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(12,636)<span></span>
</td>
<td class="text">&#160;<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) attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (976)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (8,716)<span></span>
</td>
<td class="text">&#160;<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_EarningsPerShareBasic', window );">Net income (loss) per share, basic (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0.02<span></span>
</td>
<td class="text">&#160;<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 );">Net income per share, diluted (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0.02<span></span>
</td>
<td class="text">&#160;<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_StatementOfCashFlowsAbstract', window );"><strong>Condensed Consolidated Statement of Cash Flows [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_ProfitLoss', window );">Net income (loss)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (4,896)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (12,636)<span></span>
</td>
<td class="text">&#160;<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 income (loss) to net cash provided by operating activities [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_IncreaseDecreaseInContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">42,091<span></span>
</td>
<td class="text">&#160;<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_CashAndCashEquivalentsAtCarryingValue', window );">Cash and cash equivalents at beginning of period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">84,685<span></span>
</td>
<td class="nump">84,685<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_CashAndCashEquivalentsAtCarryingValue', window );">Cash and cash equivalents at end of period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">159,184<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">159,184<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_AccountingStandardsUpdate201409Member', window );">Topic 606 [Member] | As Previously Reported Under Topic 605 [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>
</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_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [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">33,769<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">65,450<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_AccountingStandardsUpdate201409Member', window );">Topic 606 [Member] | As Previously Reported Under Topic 605 [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_us-gaap_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [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">32,890<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">60,467<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_AccountingStandardsUpdate201409Member', window );">Topic 606 [Member] | As Previously Reported Under Topic 605 [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>
</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_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [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">879<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4,983<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_AccountingStandardsUpdate201409Member', window );">Topic 606 [Member] | As Previously Reported Under Topic 605 [Member] | Research and Development 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>
</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_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [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">87,142<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">269,917<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_AccountingStandardsUpdate201409Member', window );">Topic 606 [Member] | Topic 606 Adjustment [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_us-gaap_StatementOfFinancialPositionAbstract', window );"><strong>Condensed Consolidated Balance Sheet [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_ContractWithCustomerLiabilityCurrent', window );">Current portion of deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">18,871<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_ContractWithCustomerLiabilityNoncurrent', window );">Long-term portion of deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">35,318<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_RetainedEarningsAccumulatedDeficit', window );">Accumulated deficit</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(53,636)<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(3,580)<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_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Total stockholders' equity</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(53,439)<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_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [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="num">(2,597)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11,020<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="num">(2,597)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11,020<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_ProfitLoss', window );">Net income (loss)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(2,597)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11,020<span></span>
</td>
<td class="text">&#160;<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) attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (1,635)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 11,982<span></span>
</td>
<td class="text">&#160;<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_EarningsPerShareBasic', window );">Net income (loss) per share, basic (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (0.02)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0.11<span></span>
</td>
<td class="text">&#160;<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 );">Net income per share, diluted (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (0.02)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0.11<span></span>
</td>
<td class="text">&#160;<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_StatementOfCashFlowsAbstract', window );"><strong>Condensed Consolidated Statement of Cash Flows [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_ProfitLoss', window );">Net income (loss)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (2,597)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 11,020<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_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Adjustments to reconcile net income (loss) to net cash provided by operating activities [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_IncreaseDecreaseInContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(11,020)<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_CashAndCashEquivalentsAtCarryingValue', window );">Cash and cash equivalents at beginning of period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsAtCarryingValue', window );">Cash and cash equivalents at end of period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsForNewAccountingPronouncementsAxis=us-gaap_AccountingStandardsUpdate201409Member', window );">Topic 606 [Member] | Topic 606 Adjustment [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>
</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_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [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">848<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">656<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_AccountingStandardsUpdate201409Member', window );">Topic 606 [Member] | Topic 606 Adjustment [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_us-gaap_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [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">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsForNewAccountingPronouncementsAxis=us-gaap_AccountingStandardsUpdate201409Member', window );">Topic 606 [Member] | Topic 606 Adjustment [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>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">848<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">656<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
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<td class="text">&#160;<span></span>
</td>
<td class="num">$ (3,445)<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,364<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of the effect of a change in accounting principle on revenue from the amortization of milestone payments achieved. The new revenue guidance requires the amortization of more of the milestone payments achieved, rather than recognizing the milestone payments in full during the period achieved.</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>Amount of the effect of a change in accounting principle on revenue from the amortization of milestone payments achieved. The new revenue guidance requires the use of an input method to determine the amount amortized each reporting period rather than amortizing payments evenly over the period of obligation.</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 );">- 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>
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<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>
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<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>
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<a href="javascript:void(0);" 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>
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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>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable, classified as noncurrent.</p></div>
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<a href="javascript:void(0);" 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>
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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 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>
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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 );">- 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_IncomeStatementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_IncomeStatementAbstract</td>
</tr>
<tr>
<td style="padding-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_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_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_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_NewAccountingPronouncementOrChangeInAccountingPrincipleCumulativeEffectOfChangeOnEquityOrNetAssets1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 cumulative effect of the change in accounting principle or new accounting pronouncement on retained earnings or other components of equity or net assets in the statement of financial position as of the beginning of the earliest period presented.</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 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22499-107794<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22583-107794<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22580-107794<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_NewAccountingPronouncementOrChangeInAccountingPrincipleCumulativeEffectOfChangeOnEquityOrNetAssets1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_NewAccountingPronouncementOrChangeInAccountingPrincipleRetrospectiveAdjustmentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_NewAccountingPronouncementOrChangeInAccountingPrincipleRetrospectiveAdjustmentsAbstract</td>
</tr>
<tr>
<td style="padding-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_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>
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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>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>
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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_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>
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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_StatementOfCashFlowsAbstract</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 );">- 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_StatementOfFinancialPositionAbstract</td>
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<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>
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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">
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<td><strong> Name:</strong></td>
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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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<td><strong> Name:</strong></td>
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<th class="th" colspan="4">1 Months Ended</th>
<th class="th" colspan="4">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
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<div>Dec. 31, 2017 </div>
<div>USD ($) </div>
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<th class="th">
<div>Feb. 28, 2017 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
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<th class="th">
<div>May 31, 2015 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
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<th class="th">
<div>Dec. 31, 2012 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
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<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
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<th class="th">
<div>Jun. 30, 2018 </div>
<div>Agreement</div>
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<th class="th">
<div>Sep. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2015 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Aug. 31, 2018 </div>
<div>PerformanceObligation</div>
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<div>Dec. 31, 2016 </div>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">3 months<span></span>
</td>
<td class="text">&#160;<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_ContractWithCustomerLiabilityAbstract', window );"><strong>Deferred Revenue [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_ContractWithCustomerLiabilityRevenueRecognized', window );">Revenue recognized</a></td>
<td class="text">&#160;<span></span>
</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">37,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">31,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 80,400<span></span>
</td>
<td class="nump">84,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityCurrent', window );">Current portion of deferred revenue</a></td>
<td class="nump">$ 125,336<span></span>
</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">157,145<span></span>
</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">157,145<span></span>
</td>
<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_ContractWithCustomerLiabilityNoncurrent', window );">Long-term portion of deferred revenue</a></td>
<td class="nump">108,026<span></span>
</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">523,384<span></span>
</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">523,384<span></span>
</td>
<td class="text">&#160;<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_ContractWithCustomerLiability', window );">Total deferred revenue</a></td>
<td class="nump">233,362<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_MajorCustomersAxis=ions_BiogenIncMember', window );">Biogen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<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_NumberOfAgreementsWithCollaborationPartner', window );">Number of agreements | Agreement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">12,746<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,727<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">14,232<span></span>
</td>
<td class="nump">5,639<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember', window );">SMA Collaboration with Biogen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<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="nump">$ 25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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">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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<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">$ 30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance', 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>
<td class="text">&#160;<span></span>
</td>
<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_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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>
<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember', window );">SPINRAZA [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="nump">3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_ContractWithCustomerLiabilityAbstract', window );"><strong>Deferred Revenue [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_ContractWithCustomerLiability', window );">Total deferred revenue</a></td>
<td class="nump">$ 9,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6,000<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="nump">6,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<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="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="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>
</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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<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">$ 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>
<td class="text">&#160;<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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember', window );">PTC 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">12,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">12,000<span></span>
</td>
<td class="nump">0<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_ContractWithCustomerLiability', window );">Total deferred 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="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="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>
</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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember', window );">PTC Therapeutics [Member] | TEGSEDI [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 12,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InitialApplicationPeriodCumulativeEffectTransitionAxis=us-gaap_CalculatedUnderRevenueGuidanceInEffectBeforeTopic606Member', window );">As Previously Reported Under Topic 605 [Member] | Topic 606 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</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">120,911<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">335,367<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_ContractWithCustomerLiabilityAbstract', window );"><strong>Deferred Revenue [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_ContractWithCustomerLiabilityCurrent', window );">Current portion of deferred revenue</a></td>
<td class="nump">106,465<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_ContractWithCustomerLiabilityNoncurrent', window );">Long-term portion of deferred revenue</a></td>
<td class="nump">72,708<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_ContractWithCustomerLiability', window );">Total deferred revenue</a></td>
<td class="nump">179,173<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_InitialApplicationPeriodCumulativeEffectTransitionAxis=us-gaap_CalculatedUnderRevenueGuidanceInEffectBeforeTopic606Member', window );">As Previously Reported Under Topic 605 [Member] | Topic 606 [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</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">879<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4,983<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_InitialApplicationPeriodCumulativeEffectTransitionAxis=us-gaap_DifferenceBetweenRevenueGuidanceInEffectBeforeAndAfterTopic606Member', window );">Topic 606 Adjustment [Member] | Topic 606 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(2,597)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11,020<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_ContractWithCustomerLiabilityAbstract', window );"><strong>Deferred Revenue [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_ContractWithCustomerLiabilityCurrent', window );">Current portion of deferred revenue</a></td>
<td class="nump">18,871<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_ContractWithCustomerLiabilityNoncurrent', window );">Long-term portion of deferred revenue</a></td>
<td class="nump">35,318<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_ContractWithCustomerLiability', window );">Total deferred revenue</a></td>
<td class="nump">54,189<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_InitialApplicationPeriodCumulativeEffectTransitionAxis=us-gaap_DifferenceBetweenRevenueGuidanceInEffectBeforeAndAfterTopic606Member', window );">Topic 606 Adjustment [Member] | Topic 606 [Member] | Biogen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_ContractWithCustomerLiabilityAbstract', window );"><strong>Deferred Revenue [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Total deferred revenue</a></td>
<td class="nump">24,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_InitialApplicationPeriodCumulativeEffectTransitionAxis=us-gaap_DifferenceBetweenRevenueGuidanceInEffectBeforeAndAfterTopic606Member', window );">Topic 606 Adjustment [Member] | Topic 606 [Member] | AstraZeneca [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_ContractWithCustomerLiabilityAbstract', window );"><strong>Deferred Revenue [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_ContractWithCustomerLiability', window );">Total deferred revenue</a></td>
<td class="nump">15,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_InitialApplicationPeriodCumulativeEffectTransitionAxis=us-gaap_DifferenceBetweenRevenueGuidanceInEffectBeforeAndAfterTopic606Member', window );">Topic 606 Adjustment [Member] | Topic 606 [Member] | 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_ContractWithCustomerLiabilityAbstract', window );"><strong>Deferred Revenue [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Total deferred revenue</a></td>
<td class="nump">11,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_InitialApplicationPeriodCumulativeEffectTransitionAxis=us-gaap_DifferenceBetweenRevenueGuidanceInEffectBeforeAndAfterTopic606Member', window );">Topic 606 Adjustment [Member] | Topic 606 [Member] | Other Partners [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_ContractWithCustomerLiabilityAbstract', window );"><strong>Deferred Revenue [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_ContractWithCustomerLiability', window );">Total deferred revenue</a></td>
<td class="nump">$ 2,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_InitialApplicationPeriodCumulativeEffectTransitionAxis=us-gaap_DifferenceBetweenRevenueGuidanceInEffectBeforeAndAfterTopic606Member', window );">Topic 606 Adjustment [Member] | Topic 606 [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</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">$ 848<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 656<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_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>Milestone payment earned during the period and amortized to revenue over the period of performance.</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_MilestonePaymentEarnedAndAmortizedOverPeriodOfPerformance</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_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_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_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_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_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_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_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_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>
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<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">1 Months Ended</th>
<th class="th" colspan="1">7 Months Ended</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>Oct. 31, 2018</div></th>
<th class="th"><div>Jul. 31, 2017</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Apr. 30, 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_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">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SaleOfStockPercentageOfOwnershipBeforeTransaction', window );">Percentage ownership before IPO</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="nump">68.00%<span></span>
</td>
<td class="nump">75.00%<span></span>
</td>
<td class="nump">75.00%<span></span>
</td>
<td class="nump">68.00%<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_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_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">
<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="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_ReceiptOfSharesInSubsidiary', window );">Additional shares of Akcea stock received when TEGSEDI received marketing authorization in the U.S. (in shares)</a></td>
<td class="nump">1.7<span></span>
</td>
<td class="text">&#160;<span></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 when TEGSEDI received marketing authorization in one or more countries or approval from a government agency, such as the Food and Drug Administration (FDA).</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>
</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_NoncontrollingInterestAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_NoncontrollingInterestAbstract</td>
</tr>
<tr>
<td style="padding-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_SaleOfStockPercentageOfOwnershipBeforeTransaction">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 subsidiary's or equity investee's stock owned by parent company before stock transaction.</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_SaleOfStockPercentageOfOwnershipBeforeTransaction</td>
</tr>
<tr>
<td style="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_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>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
</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>
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<DOCUMENT>
<TYPE>XML
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<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;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6829898720">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)<br></strong></div></th>
<th class="th">
<div>Sep. 30, 2018 </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">1<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
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<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_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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</div></td></tr>
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</body>
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</DOCUMENT>
<DOCUMENT>
<TYPE>XML
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<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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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6829893872">
<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">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 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_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract', window );"><strong>Inventory Valuation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InventoryWriteDown', window );">Inventory write-off</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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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<tr>
<td style="padding-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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryWriteDown">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 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>
<td style="white-space:nowrap;">us-gaap_InventoryWriteDown</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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>
</div>
</body>
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</TEXT>
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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6835439408">
<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="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 30, 2017</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 30, 2017</div></th>
<th class="th"><div>Dec. 31, 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_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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_PreferredStockDividendRatePercentage', window );">Dividend rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertiblePreferredStockTermsOfConversion', window );">Conversion ratio</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">converted into common stock on a 1:1 basis<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="num">$ (0.03)<span></span>
</td>
<td class="num">$ (0.02)<span></span>
</td>
<td class="num">$ (0.33)<span></span>
</td>
<td class="nump">$ 0.13<span></span>
</td>
<td class="text">&#160;<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="num">$ (4,559)<span></span>
</td>
<td class="num">$ (2,611)<span></span>
</td>
<td class="num">$ (46,335)<span></span>
</td>
<td class="nump">$ 3,266<span></span>
</td>
<td class="text">&#160;<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="num">$ (4,616)<span></span>
</td>
<td class="num">$ (1,976)<span></span>
</td>
<td class="num">$ (43,162)<span></span>
</td>
<td class="nump">$ 16,321<span></span>
</td>
<td class="text">&#160;<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">143,314<span></span>
</td>
<td class="nump">124,370<span></span>
</td>
<td class="nump">132,518<span></span>
</td>
<td class="nump">123,746<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 16,321<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</a></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">24<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">143,314<span></span>
</td>
<td class="nump">124,370<span></span>
</td>
<td class="nump">132,518<span></span>
</td>
<td class="nump">125,858<span></span>
</td>
<td class="text">&#160;<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="num">$ (0.03)<span></span>
</td>
<td class="num">$ (0.02)<span></span>
</td>
<td class="num">$ (0.33)<span></span>
</td>
<td class="nump">$ 0.13<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>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes275PercentMember', window );">2 3/4 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<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_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">2.75%<span></span>
</td>
<td class="nump">2.75%<span></span>
</td>
<td class="nump">2.75%<span></span>
</td>
<td class="nump">2.75%<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_EmployeeStockOptionMember', window );">Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,658<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">430<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>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">$ 43,226<span></span>
</td>
<td class="nump">$ 10,144<span></span>
</td>
<td class="nump">$ 67,517<span></span>
</td>
<td class="nump">$ 100,235<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>
</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>
<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="num">$ (47,843)<span></span>
</td>
<td class="num">$ (12,120)<span></span>
</td>
<td class="num">$ (110,680)<span></span>
</td>
<td class="num">$ (83,914)<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] | Preferred 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>
<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>
<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_WeightedAverageNumberOfSharesOwnedInSubsidiary', window );">Weighted average shares owned in Akcea (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5,651<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">21,055<span></span>
</td>
<td class="text">&#160;<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_EarningsPerShareBasic', window );">Basic net income (loss) per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (0.01)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (2.16)<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="num">$ (57)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (45,479)<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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">65,538<span></span>
</td>
<td class="nump">36,556<span></span>
</td>
<td class="nump">57,347<span></span>
</td>
<td class="nump">12,319<span></span>
</td>
<td class="text">&#160;<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="num">$ (0.73)<span></span>
</td>
<td class="num">$ (0.33)<span></span>
</td>
<td class="num">$ (1.93)<span></span>
</td>
<td class="num">$ (3.12)<span></span>
</td>
<td class="text">&#160;<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="num">$ (47,843)<span></span>
</td>
<td class="num">$ (12,063)<span></span>
</td>
<td class="num">$ (110,680)<span></span>
</td>
<td class="num">$ (38,435)<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_ConvertiblePreferredStockTermsOfConversion">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>Specific terms relevant to convertibility. Includes class of preferred stock and number of shares convertible into, exercise (or conversion) price or rates, dates relevant to conversion timing and events relevant to conversion. Describe also any beneficial conversion features. where convertible preferred stock with a nondetachable conversion feature is in-the-money at commitment date. For contingently convertible preferred stock, discuss the circumstances of the contingency, including the events or changes in circumstance that would cause the contingency to be met and any of the significant features necessary to understand the conversion rights and the timing of those rights. Include also an events or changes in circumstance, if any, that could adjust or change the contingency, conversion price, or number of shares, including significant terms of those changes.</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 8<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21538-112644<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(28))<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 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21521-112644<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(27))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21506-112644<br><br>Reference 6: 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 3<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21475-112644<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_ConvertiblePreferredStockTermsOfConversion</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>
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<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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<td>xbrli:monetaryItemType</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; 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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<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>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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 rate used to calculate dividend payments on preferred 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;">us-gaap_PreferredStockDividendRatePercentage</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<a href="javascript:void(0);" onclick="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 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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</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_WeightedAverageNumberOfSharesOutstandingBasic</td>
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<td><strong> Balance Type:</strong></td>
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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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember</td>
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<td><strong> Name:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6849725808">
<tr>
<th class="tl" colspan="2" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Accumulated Other Comprehensive Loss (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 30, 2017</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 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_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract', window );"><strong>Accumulated Other Comprehensive Income (Loss) [Roll Forward]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Beginning balance</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 365,280<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_OtherComprehensiveIncomeLossNetOfTax', window );">Net current period other comprehensive income (loss)</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 105<span></span>
</td>
<td class="nump">$ 173<span></span>
</td>
<td class="num">(773)<span></span>
</td>
<td class="nump">$ 159<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_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Ending balance</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">840,144<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">840,144<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_StatementEquityComponentsAxis=us-gaap_AociIncludingPortionAttributableToNoncontrollingInterestMember', window );">Accumulated Other Comprehensive Loss [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract', window );"><strong>Accumulated Other Comprehensive Income (Loss) [Roll Forward]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Beginning balance</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(32,637)<span></span>
</td>
<td class="num">(30,372)<span></span>
</td>
<td class="num">(31,759)<span></span>
</td>
<td class="num">(30,358)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Ending balance</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(32,532)<span></span>
</td>
<td class="num">(30,199)<span></span>
</td>
<td class="num">(32,532)<span></span>
</td>
<td class="num">(30,199)<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_StatementEquityComponentsAxis=us-gaap_AccumulatedNetInvestmentGainLossIncludingPortionAttributableToNoncontrollingInterestMember', window );">Unrealized Gains (Losses) on Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract', window );"><strong>Accumulated Other Comprehensive Income (Loss) [Roll Forward]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax', window );">Other comprehensive income (loss) before reclassifications</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">133<span></span>
</td>
<td class="nump">215<span></span>
</td>
<td class="num">(834)<span></span>
</td>
<td class="nump">610<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_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTax', window );">Amounts reclassified from accumulated other comprehensive loss</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(374)<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_OtherComprehensiveIncomeLossTax', window );">Other comprehensive income (loss), tax</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<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_StatementEquityComponentsAxis=us-gaap_AccumulatedForeignCurrencyAdjustmentIncludingPortionAttributableToNoncontrollingInterestMember', window );">Currency Translation Adjustment [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract', window );"><strong>Accumulated Other Comprehensive Income (Loss) [Roll Forward]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax', window );">Other comprehensive income (loss) before reclassifications</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">$ (28)<span></span>
</td>
<td class="num">$ (42)<span></span>
</td>
<td class="nump">$ 61<span></span>
</td>
<td class="num">$ (77)<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">There was no income tax expense or benefit related to elements of other comprehensive income (loss) for the three and nine months ended September 30, 2018 and 2017.</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_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 other comprehensive 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 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 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 55<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=109228884&amp;loc=d3e1436-108581<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_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_OtherComprehensiveIncomeLossNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 other comprehensive income (loss).</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 (b)<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 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 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 55<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=109228884&amp;loc=d3e1436-108581<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_OtherComprehensiveIncomeLossNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_OtherComprehensiveIncomeLossTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 tax expense (benefit) allocated to other comprehensive 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 20<br> -Section 45<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109238882&amp;loc=d3e39076-109324<br><br>Reference 2: 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 (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=109238882&amp;loc=d3e38679-109324<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 12<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=d3e640-108580<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_OtherComprehensiveIncomeLossTax</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>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 reclassification adjustments of other comprehensive income (loss).</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 17B<br> -URI http://asc.fasb.org/extlink&amp;oid=114867106&amp;loc=SL34724394-108580<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 55<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=109228884&amp;loc=d3e1436-108581<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_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTax</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>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_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract</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_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>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StatementEquityComponentsAxis=us-gaap_AociIncludingPortionAttributableToNoncontrollingInterestMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_StatementEquityComponentsAxis=us-gaap_AociIncludingPortionAttributableToNoncontrollingInterestMember</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>
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</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StatementEquityComponentsAxis=us-gaap_AccumulatedNetInvestmentGainLossIncludingPortionAttributableToNoncontrollingInterestMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_StatementEquityComponentsAxis=us-gaap_AccumulatedNetInvestmentGainLossIncludingPortionAttributableToNoncontrollingInterestMember</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>
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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_StatementEquityComponentsAxis=us-gaap_AccumulatedForeignCurrencyAdjustmentIncludingPortionAttributableToNoncontrollingInterestMember</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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<head>
<title></title>
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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6827715824">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Segment Information (Details)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr><th class="th">
<div>Sep. 30, 2018 </div>
<div>Segment</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_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NumberOfOperatingSegments', window );">Number of operating segments</a></td>
<td class="nump">2<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_NumberOfOperatingSegments">
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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 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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NumberOfOperatingSegments</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
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<tr>
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<td>na</td>
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<td>duration</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_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract</td>
</tr>
<tr>
<td style="padding-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>42
<FILENAME>R30.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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<body>
<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6846484720">
<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>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 30, 2017</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 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_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 34,883<span></span>
</td>
<td class="nump">$ 21,472<span></span>
</td>
<td class="nump">$ 97,210<span></span>
</td>
<td class="nump">$ 63,642<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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">18,780<span></span>
</td>
<td class="nump">16,181<span></span>
</td>
<td class="nump">57,698<span></span>
</td>
<td class="nump">48,443<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">16,103<span></span>
</td>
<td class="nump">5,291<span></span>
</td>
<td class="nump">$ 39,512<span></span>
</td>
<td class="nump">$ 15,199<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2.30%<span></span>
</td>
<td class="nump">1.80%<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">63.10%<span></span>
</td>
<td class="nump">66.10%<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">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">4 years 7 months 6 days<span></span>
</td>
<td class="text">4 years 6 months<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">139,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 139,500<span></span>
</td>
<td class="text">&#160;<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">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year 3 months 18 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=ions_BoardOfDirectorStockOptionMember', window );">Board of Director Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2.80%<span></span>
</td>
<td class="nump">2.20%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">61.50%<span></span>
</td>
<td class="nump">61.20%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">6 years 7 months 6 days<span></span>
</td>
<td class="text">6 years 7 months 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_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockMember', window );">ESPP [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.80%<span></span>
</td>
<td class="nump">0.80%<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">47.30%<span></span>
</td>
<td class="nump">59.90%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">6 months<span></span>
</td>
<td class="text">6 months<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">32,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 32,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year 7 months 6 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 51.83<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] | Board of Directors [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<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_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted-average grant date fair value (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 42.88<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">$ 12,700<span></span>
</td>
<td class="nump">$ 4,700<span></span>
</td>
<td class="nump">$ 31,200<span></span>
</td>
<td class="nump">$ 11,800<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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td>duration</td>
</tr>
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</div></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 );">- 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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td>duration</td>
</tr>
</table></div>
</div></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 );">- 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>
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</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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</div></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 );">- 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>
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<td>xbrli:durationItemType</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>
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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>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>
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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 );">- 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>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</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_ShareBasedCompensationAbstract</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>
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<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>
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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 );">- 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>
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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 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>
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<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_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>
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<td><strong> Data Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
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<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>
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<td><strong> Data Type:</strong></td>
<td>num:perShareItemType</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>
</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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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
</div></td></tr>
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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>
<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_IncomeStatementLocationAxis=ions_ResearchDevelopmentAndPatentMember</td>
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<td>na</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember</td>
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<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
<td></td>
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</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=ions_BoardOfDirectorStockOptionMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=ions_BoardOfDirectorStockOptionMember</td>
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<td></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_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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<td></td>
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<td>na</td>
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<td></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_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis=ions_EmployeeMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
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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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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RelatedPartyTransactionsByRelatedPartyAxis=ions_BoardOfDirectorsMember</td>
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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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember</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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<DOCUMENT>
<TYPE>XML
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<FILENAME>R31.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;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6836219456">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments, Contract Maturity of Available-for-Sale Securities (Details)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr><th class="th">
<div>Sep. 30, 2018 </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">80.00%<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">15.00%<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">1<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_invest_InvestmentsScheduleAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>invest_</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_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>
<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_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 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>
</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_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>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</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>
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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>
</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_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>44
<FILENAME>R32.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6850265072">
<tr>
<th class="tl" colspan="2" rowspan="1"><div style="width: 200px;"><strong>Investments, Summary of Investments (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Dec. 31, 2017</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_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="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_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="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_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">$ 1,502,739<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 911,594<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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">41<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">14<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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(3,942)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(3,072)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">1,498,838<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">908,536<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="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_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="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_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">1,188,558<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">643,193<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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">25<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">6<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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(1,852)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(1,103)<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_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,186,731<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">642,096<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="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_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="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_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">314,181<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">268,401<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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">16<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">8<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">(2,090)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(1,969)<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_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">312,107<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">266,440<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="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_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="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_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">841,397<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">500,599<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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">23<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">2<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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(1,264)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(752)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">840,156<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">499,849<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="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_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="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_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">240,208<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">148,663<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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">16<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">8<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">(1,420)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(1,059)<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_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">238,804<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">147,612<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="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_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="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_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">143,008<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">83,926<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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2<span></span>
</td>
<td class="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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(169)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(212)<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_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">142,841<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">83,714<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="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_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="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_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">32,435<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">52,779<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_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="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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(109)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(168)<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_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">32,326<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">52,611<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="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_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="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_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">154,280<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">29,428<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_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="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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(89)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(17)<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_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">154,191<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">29,411<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="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_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="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_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">9,872<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">1,409<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_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="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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(10)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(2)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">9,862<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,407<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="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_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="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_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1],[2]</sup></td>
<td class="nump">49,873<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">29,240<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_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">4<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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(330)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(122)<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_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">49,543<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">29,122<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="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_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="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_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">31,666<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">65,550<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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="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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(551)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(740)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">$ 31,115<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 64,810<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_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>
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<td><strong> Balance Type:</strong></td>
<td>credit</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>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>
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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>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>
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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 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>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
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</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 );">- 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>
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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_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember</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>
</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_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfOneYearOrLessMember">
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<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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<tr>
<td><strong> Period Type:</strong></td>
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<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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<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 border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember">
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<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>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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</table></div>
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<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_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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<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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<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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<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>
</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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<DOCUMENT>
<TYPE>XML
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<FILENAME>R33.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
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<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;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6833447328">
<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>Sep. 30, 2018 </div>
<div>USD ($) </div>
<div>Investment</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">626<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 1,211,143<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">(2,116)<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">162,315<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">(1,826)<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">1,373,458<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">$ (3,942)<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_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">495<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">$ 889,172<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">(1,687)<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">83,706<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_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">Unrealized losses, more than 12 months of temporary impairment</a></td>
<td class="num">(997)<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">972,878<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">$ (2,684)<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">51<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">$ 132,231<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">(139)<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">26,862<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">Unrealized losses, more than 12 months of temporary impairment</a></td>
<td class="num">(139)<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">159,093<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">$ (278)<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">32<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">$ 164,053<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">(99)<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">164,053<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">$ (99)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">48<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">$ 25,687<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">(191)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue', window );">Estimated fair value, more than 12 months of temporary impairment</a></td>
<td class="nump">51,747<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">(690)<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">77,434<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">$ (881)<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td>instant</td>
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<tr><td><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>
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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>na</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 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>
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<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>
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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>
</tr>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
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<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>
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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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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
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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>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>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
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<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>
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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>
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<td>instant</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 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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<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>
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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_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember</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>
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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>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>na</td>
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<tr>
<td><strong> Name:</strong></td>
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<th class="tl" colspan="2" rowspan="1"><div style="width: 200px;"><strong>Fair Value Measurements, Fair Value Measurements on a Recurring Basis (Details) - USD ($)<br> $ in Thousands</strong></div></th>
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<td class="text">&#160;<span></span>
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</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">395,649<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 86,262<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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">1,894,487<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">994,798<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</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>
</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">1,078,960<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">647,461<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></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>
</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>
</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">19,700<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</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>
</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>
</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>[3]</sup></td>
<td class="nump">175,167<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">136,325<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</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>
</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>[3]</sup></td>
<td class="nump">164,053<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">30,818<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</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>
</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">80,658<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">93,932<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4]</sup></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] | 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>
</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>
</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="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">3,500<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</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>
</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_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">395,649<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">86,262<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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">559,702<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">117,080<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</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>
</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>
</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>
</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>
</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>
</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>
</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>
</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">164,053<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">30,818<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</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>
</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>
</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>
</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>
</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_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>
</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">1,334,785<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">877,718<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</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>
</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">1,078,960<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">647,461<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</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>
</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">175,167<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">136,325<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</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>
</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>
</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>
</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>
</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">$ 80,658<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 93,932<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr><td colspan="6"></td></tr>
<tr><td colspan="6"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">Included in cash and cash equivalents 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">At September 30, 2018, $19.7 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">[3]</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">[4]</td>
<td style="vertical-align: top;" valign="top">At December 31, 2017, $3.5 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>
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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>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>
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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>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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FairValueAssetsLevel1ToLevel2TransfersAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 transfers of assets measured on a recurring basis out of Level 1 of the fair value hierarchy into Level 2.</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 (bb)<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_FairValueAssetsLevel1ToLevel2TransfersAmount</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>
<td>instant</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FairValueAssetsLevel2ToLevel1TransfersAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 transfers of assets measured on a recurring basis out of Level 2 of the fair value hierarchy into Level 1.</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 (bb)<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_FairValueAssetsLevel2ToLevel1TransfersAmount</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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<td><strong> Period Type:</strong></td>
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</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 );">- 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_FairValueDisclosuresAbstract</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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<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_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>
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<td><strong> Balance Type:</strong></td>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>
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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_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember</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></td>
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</div></td></tr>
</table>
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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_BalanceSheetLocationAxis=us-gaap_CashAndCashEquivalentsMember</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>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember</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_FinancialInstrumentAxis=us-gaap_USTreasurySecuritiesMember</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_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember</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_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel1Member</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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<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>
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<td><strong> Balance Type:</strong></td>
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<DOCUMENT>
<TYPE>XML
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<head>
<title></title>
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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6846481344">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fair Value Measurements, Fair Value Measurements Using Significant Unobservable Inputs (Level 3) (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">9 Months Ended</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>Sep. 30, 2017</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Dec. 31, 2017</div></th>
<th class="th"><div>Jan. 31, 2017</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_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>
<td class="text">&#160;<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_FutureStockPurchaseAbstract', window );"><strong>Novartis Future Stock Purchase [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_PotentialFuturePremium', window );">Fair value of potential future premium</a></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">$ 5,000<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>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel2Member', window );">Significant Other Observable Inputs (Level 2) [Member] | 1 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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="text">&#160;<span></span>
</td>
<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_NotesPayableFairValueDisclosure', window );">Fair value of convertible notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 725,700<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_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel3Member', window );">Significant Unobservable Inputs (Level 3) [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Financial instruments</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | 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>
<td class="text">&#160;<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_FutureStockPurchaseAbstract', window );"><strong>Novartis Future Stock Purchase [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_AdditionalAmountOfCommonStockRequiredToBePurchased', window );">Additional amount of common stock required to be purchased</a></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">$ 50,000<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_FairValueByAssetClassAxis=ions_PotentialFuturePremiumMember', window );">Potential Future Premium [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward', window );"><strong>Unobservable Inputs (Level 3) [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>
</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_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetValue', window );">Beginning balance of Level 3 instruments</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>
</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_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetTransfersIntoLevel3', window );">Value of the potential premium we would have received from Novartis at inception of the SPA (January 2017)</a></td>
<td class="nump">5,035<span></span>
</td>
<td class="text">&#160;<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_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetGainLossIncludedInEarnings1', window );">Recurring fair value adjustment during the nine months ended September 30, 2017</a></td>
<td class="num">(5,035)<span></span>
</td>
<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_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetValue', window );">Ending balance of Level 3 instruments</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>
</tr>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AdditionalAmountOfCommonStockRequiredToBePurchased">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 common stock the collaboration partner is required to purchase under a Stock Purchase Agreement (SPA) in conjunction with 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_AdditionalAmountOfCommonStockRequiredToBePurchased</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_FutureStockPurchaseAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_FutureStockPurchaseAbstract</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_PotentialFuturePremium">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 fair value of the potential future premium the Company will receive if Novartis purchases its common stock under a Stock Purchase Agreement (SPA) entered into in January 2017.</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_PotentialFuturePremium</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_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>
</tr>
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<td><strong> Data Type:</strong></td>
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<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>
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<tr>
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<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>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of gain (loss) recognized in the income statement for financial instrument classified as an asset measured using unobservable inputs that reflect the entity's own assumption about the assumptions market participants would use in pricing.</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 (c)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=99377789&amp;loc=d3e19207-110258<br></p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of transfer of financial instrument classified as an asset into level 3 of the fair value hierarchy.</p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Fair value of financial instrument classified as an asset measured using unobservable inputs that reflect the entity's own assumption about the assumptions market participants would use in pricing.</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 (c)<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">
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<td><strong> Name:</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>
<td><strong> Name:</strong></td>
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<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">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Other Obligations, Line of Credit Arrangement (Details)<br> $ in Millions</strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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</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_LineOfCreditFacilityUnusedCapacityCommitmentFeePercentage', window );">Commitment fee percentage on unused capacity</a></td>
<td class="nump">0.25%<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_LineOfCreditFacilityAxis=ions_MorganStanleyPrivateBankNationalAssociationMember', window );">Morgan Stanley [Member] | Revolving Line of Credit [Member] | LIBOR [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_LineOfCreditFacilityAbstract', window );"><strong>Line of Credit Arrangement [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_TermOfVariableRate', window );">Term of variable rate</a></td>
<td class="text">1 month<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_DebtInstrumentBasisSpreadOnVariableRate1', window );">Basis spread on variable rate</a></td>
<td class="nump">1.25%<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_DebtInstrumentDescriptionOfVariableRateBasis', window );">Term of fixed rate elected</a></td>
<td class="text">one, two, three, four, six, or twelve 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_TermOfVariableRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 the variable 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>
<a href="javascript:void(0);" 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_TermOfVariableRate</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_DebtInstrumentBasisSpreadOnVariableRate1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 points added to the reference rate to compute the variable rate on the debt 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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentBasisSpreadOnVariableRate1</td>
</tr>
<tr>
<td style="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_DebtInstrumentDescriptionOfVariableRateBasis">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 reference rate for the variable rate of the debt instrument, such as LIBOR or the US Treasury rate and the maturity of the reference rate used, such as three months or six months LIBOR.</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_DebtInstrumentDescriptionOfVariableRateBasis</td>
</tr>
<tr>
<td style="padding-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_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_DebtInstrumentMaturityDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>Date when the debt instrument is scheduled to be fully repaid, in CCYY-MM-DD format.</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 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(2))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 820<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)<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_DebtInstrumentMaturityDate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:dateItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentTerm">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 between issuance and maturity of debt instrument, 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;">us-gaap_DebtInstrumentTerm</td>
</tr>
<tr>
<td style="padding-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_LineOfCredit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 carrying value as of the balance sheet date of the current and noncurrent portions of long-term obligations drawn from a line of credit, which is a bank's commitment to make loans up to a specific amount. Examples of items that might be included in the application of this element may consist of letters of credit, standby letters of credit, and revolving credit arrangements, under which borrowings can be made up to a maximum amount as of any point in time conditional on satisfaction of specified terms before, as of and after the date of drawdowns on the line. Includes short-term obligations that would normally be classified as current liabilities but for which (a) postbalance sheet date issuance of a long term obligation to refinance the short term obligation on a long term basis, or (b) the enterprise has entered into a financing agreement that clearly permits the enterprise to refinance the short-term obligation on a long term basis and the following conditions are met (1) the agreement does not expire within 1 year and is not cancelable by the lender except for violation of an objectively determinable provision, (2) no violation exists at the BS date, and (3) the lender has entered into the financing agreement is expected to be financially capable of honoring the 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))<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(16))<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_LineOfCredit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_LineOfCreditFacilityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_LineOfCreditFacilityAbstract</td>
</tr>
<tr>
<td style="padding-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_LineOfCreditFacilityMaximumBorrowingCapacity">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>Maximum borrowing capacity under the credit facility without consideration of any current restrictions on the amount that could be borrowed or the amounts currently outstanding under the facility.</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(b),22(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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_LineOfCreditFacilityUnusedCapacityCommitmentFeePercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 fee, expressed as a percentage of the line of credit facility, for available but unused credit capacity under the credit facility.</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_LineOfCreditFacilityUnusedCapacityCommitmentFeePercentage</td>
</tr>
<tr>
<td style="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_DebtInstrumentAxis=ions_FixedRateNoteWithMorganStanleyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_FixedRateNoteWithMorganStanleyMember</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_LineOfCreditFacilityAxis=ions_MorganStanleyPrivateBankNationalAssociationMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_LineOfCreditFacilityAxis=ions_MorganStanleyPrivateBankNationalAssociationMember</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_CreditFacilityAxis=us-gaap_RevolvingCreditFacilityMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_CreditFacilityAxis=us-gaap_RevolvingCreditFacilityMember</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_VariableRateAxis=us-gaap_LondonInterbankOfferedRateLIBORMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_VariableRateAxis=us-gaap_LondonInterbankOfferedRateLIBORMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
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</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>49
<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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</head>
<body>
<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6830001408">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Other Obligations, Research and Development and Manufacturing Facilities (Details) - USD ($)<br> $ in Millions</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Jul. 31, 2017</div></th>
<th class="th"><div>Sep. 30, 2018</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_PropertyPlantAndEquipmentByTypeAxis=ions_PrimaryResearchAndDevelopmentFacilityMember', window );">Primary R&amp;D Facility [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_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Research and Development and Manufacturing Facilities [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_PaymentsToAcquireBuildings', window );">Payment to acquire building</a></td>
<td class="nump">$ 79.4<span></span>
</td>
<td class="text">&#160;<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_ProceedsFromLoanOriginations1', window );">Proceeds from mortgage loan</a></td>
<td class="nump">$ 51.3<span></span>
</td>
<td class="text">&#160;<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</a></td>
<td class="nump">3.88%<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_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan', window );">Period to make interest only payments on mortgage loan</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<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=us-gaap_ManufacturingFacilityMember', window );">Manufacturing Facility [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_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Research and Development and Manufacturing Facilities [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_PaymentsToAcquireBuildings', window );">Payment to acquire building</a></td>
<td class="nump">$ 14.0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromLoanOriginations1', window );">Proceeds from mortgage loan</a></td>
<td class="nump">$ 9.1<span></span>
</td>
<td class="text">&#160;<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</a></td>
<td class="nump">4.20%<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_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan', window );">Period to make interest only payments on mortgage loan</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 to make only payments of interest on the mortgage loan, 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_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan</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_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_PaymentsToAcquireBuildings">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 buildings (properties) whether for investment or use.</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 (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3213-108585<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_PaymentsToAcquireBuildings</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_PaymentsToAcquirePropertyPlantAndEquipmentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_PaymentsToAcquirePropertyPlantAndEquipmentAbstract</td>
</tr>
<tr>
<td style="padding-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_ProceedsFromLoanOriginations1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>Cash inflow associated with loan origination (the process when securing a mortgage for a piece of real property) or lease origination.</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 12<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3179-108585<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_ProceedsFromLoanOriginations1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_PropertyPlantAndEquipmentByTypeAxis=ions_PrimaryResearchAndDevelopmentFacilityMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_PrimaryResearchAndDevelopmentFacilityMember</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_PropertyPlantAndEquipmentByTypeAxis=us-gaap_ManufacturingFacilityMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_ManufacturingFacilityMember</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>R38.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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<body>
<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6856556608">
<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="5">1 Months Ended</th>
<th class="th" colspan="3">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Apr. 30, 2018 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2017 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Jul. 31, 2016 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2013 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2012 </div>
<div>USD ($) </div>
<div>PerformanceObligation </div>
<div>Target </div>
<div>Program</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($) </div>
<div>Drug</div>
</th>
<th class="th">
<div>Jun. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($) </div>
<div>Drug</div>
</th>
<th class="th">
<div>Sep. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2017 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2016 </div>
<div>PerformanceObligation</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 145,395<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 118,314<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
<td class="nump">$ 346,387<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="text">&#160;<span></span>
</td>
<td class="nump">$ 233,362<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 233,362<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70,010<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">32,890<span></span>
</td>
<td class="nump">167,743<span></span>
</td>
<td class="nump">60,467<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 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 62,639<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">83,697<span></span>
</td>
<td class="nump">$ 225,584<span></span>
</td>
<td class="nump">280,281<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_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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6<span></span>
</td>
<td class="text">&#160;<span></span>
</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="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " 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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">104,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 87,800<span></span>
</td>
<td class="nump">234,600<span></span>
</td>
<td class="nump">$ 197,600<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="text">&#160;<span></span>
</td>
<td class="nump">$ 93,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 593,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 593,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">93,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">72.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">74.00%<span></span>
</td>
<td class="nump">58.00%<span></span>
</td>
<td class="nump">57.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 70,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 32,900<span></span>
</td>
<td class="nump">$ 167,700<span></span>
</td>
<td class="nump">$ 60,500<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_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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">34,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 54,900<span></span>
</td>
<td class="nump">66,900<span></span>
</td>
<td class="nump">$ 137,100<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember', window );">SPINRAZA [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax', window );">Cumulative revenue earned</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">717,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 717,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember', window );">SPINRAZA [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_RoyaltyPercentageReceivedOnNetSalesOfDrug', window );">Royalty percentage received on net sales of drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember', window );">SPINRAZA [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_RoyaltyPercentageReceivedOnNetSalesOfDrug', window );">Royalty percentage received on net sales of drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">15.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember', window );">SPINRAZA [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax', window );">Cumulative revenue earned</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">281,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 281,000<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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember', window );">SPINRAZA [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax', window );">Cumulative revenue earned</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">436,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">436,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 90,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</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">58,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">58,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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>
<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_NumberOfTargets', window );">Number of targets | Target</a></td>
<td class="text">&#160;<span></span>
</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">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="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_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized', window );">Number of programs under which drugs are to be developed and commercialized | Program</a></td>
<td class="text">&#160;<span></span>
</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">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="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="text">&#160;<span></span>
</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">$ 30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_NextPotentialPayment', window );">Next prospective payment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">7,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
</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_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments', window );">Maximum amount of payments receivable per program for license fee and substantive milestone payments</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">210,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">210,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones', window );">Maximum amount of payments receivable per program for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones', window );">Maximum amount of payments receivable per program for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">130,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">130,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember', window );">Neurology [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_PaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">40,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">40,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">170,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">170,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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>
<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">$ 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>
<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_NextPotentialPayment', window );">Next prospective payment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
<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_NumberOfDrugsCurrentlyBeingAdvanced', window );">Number of drugs currently being advanced | Drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">5<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_PaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">145,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 145,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member] | Antisense Molecule [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones', window );">Maximum amount of payments receivable for license fees and substantive milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">260,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">260,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">130,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">130,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member] | Other Modalities [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones', window );">Maximum amount of payments receivable for license fees and substantive milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">90,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">90,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
</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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">55,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 55,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember', window );">New Antisense Drugs for the Treatment of SMA [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_RoyaltyPercentageReceivedOnNetSalesOfDrug', window );">Royalty percentage received on net sales of drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<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">$ 25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones', window );">Maximum amount of payments receivable for license fees and substantive milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">80,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">80,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones', window );">Maximum amount of payments receivable for commercialization milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">180,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">180,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForSalesMilestones', window );">Maximum amount of payments receivable for sales milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NextPotentialPayment', window );">Next prospective payment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_RoyaltyPercentageReceivedOnNetSalesOfDrug', window );">Royalty percentage received on net sales of drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 375,000<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="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_NextPotentialPayment', window );">Next prospective payment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">7,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
</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_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 552,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments', window );">Maximum amount of payments receivable per program for license fee and substantive milestone payments</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 270,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 270,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_TermOfCollaborationAgreement', window );">Term of collaboration agreement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_UpfrontPaymentReceivedIncludingPurchaseOfStock', window );">Upfront payment received, including purchase of stock</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfCommonStock', window );">Proceeds from issuance of common stock</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 625,000<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="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_PercentageCashPremiumPaidOnSharesPurchased', window );">Percentage cash premium paid on shares purchased</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_PremiumPaidOnSharesPurchased', window );">Premium paid on shares purchased</a></td>
<td class="nump">$ 177,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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, 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>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_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax</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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for commercialization milestones 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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for development milestones 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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for license fees and substantive milestones 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_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for regulatory milestones 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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForSalesMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for sales milestones 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_MaximumAmountOfPaymentsReceivableForSalesMilestones</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_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable per drug or program for development milestone payments 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_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones</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_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable per drug or program for license fees and/or substantive milestone payments 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_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments</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_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable per drug or program for regulatory milestone payments 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_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPotentialPayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 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_NextPotentialPayment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_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>
</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_NumberOfDrugsCurrentlyBeingAdvanced">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 drugs currently being advanced 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_NumberOfDrugsCurrentlyBeingAdvanced</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_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 programs under which drugs are to be developed and commercialized 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_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized</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_NumberOfTargets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 targets for the research and development of drugs 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_NumberOfTargets</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_PaymentsIncludedInTransactionPriceForPerformanceObligation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 payments received since inception of the collaboration agreement included in the transaction price for the performance obligation.</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_PaymentsIncludedInTransactionPriceForPerformanceObligation</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_PercentageCashPremiumPaidOnSharesPurchased">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 cash premium paid per share of the Company's common 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_PercentageCashPremiumPaidOnSharesPurchased</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>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PremiumPaidOnSharesPurchased">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 premium paid on the purchase of the Company's common 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_PremiumPaidOnSharesPurchased</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_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 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_RoyaltyPercentageReceivedOnNetSalesOfDrug">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>Royalty percentage received on the net sales of a drug by a collaboration partner 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_RoyaltyPercentageReceivedOnNetSalesOfDrug</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>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_TermOfCollaborationAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 the collaboration agreement, 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_TermOfCollaborationAgreement</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_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_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>
</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_ProceedsFromIssuanceOfCommonStock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 inflow from the additional capital contribution to the entity.</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 14<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109223946&amp;loc=d3e3255-108585<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">
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<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>
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<div>USD ($)</div>
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<div>USD ($)</div>
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</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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="text">&#160;<span></span>
</td>
<td class="nump">$ 145,395<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 118,314<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
<td class="nump">$ 346,387<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 233,362<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="nump">62,639<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 83,697<span></span>
</td>
<td class="nump">225,584<span></span>
</td>
<td class="nump">$ 280,281<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_CollaborativeArrangementsAndLicensingAgreementsAstraZenecaMember', window );">AstraZeneca [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 44,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 44,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 57,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsAstraZenecaMember', window );">AstraZeneca [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4.00%<span></span>
</td>
<td class="nump">21.00%<span></span>
</td>
<td class="nump">4.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsAstraZenecaMember', window );">AstraZeneca [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="nump">$ 14,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 4,800<span></span>
</td>
<td class="nump">$ 86,500<span></span>
</td>
<td class="nump">$ 14,800<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstraZenecaMember', window );">Cardiac, Renal and Metabolic Diseases [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_NumberOfDrugsThatCanBeLicensedUnderOptionInCollaborationAgreements', window );">Number of drugs that can be licensed under option in collaboration agreements | Drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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">$ 65,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones', window );">Minimum amount of payments receivable for license fees and substantive milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,100,000<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="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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></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">2,900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">165,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">165,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NextPotentialPayment', window );">Next prospective payment</a></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>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></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>
<td class="text">&#160;<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_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 65,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="nump">10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstraZenecaMember', window );">Cardiac, Renal and Metabolic Diseases [Member] | IONIS-AZ5-2.5 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstraZenecaMember', window );">Cardiac, Renal and Metabolic Diseases [Member] | IONIS-AZ6-2.5 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstraZenecaMember', window );">Cardiac, Renal and Metabolic Diseases [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_PaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">90,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">90,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstraZenecaMember', window );">Oncology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="nump">$ 31,000<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="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_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones', window );">Minimum amount of payments receivable for license fees and substantive milestones</a></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">450,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">450,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></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">152,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">152,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></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">275,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">275,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments 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">97,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">97,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_NextPotentialPayment', window );">Next prospective payment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 31,000<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_NumberOfObligationsFullySatisified', window );">Number of obligations fully satisfied | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstraZenecaMember', window );">Oncology [Member] | Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_NumberOfProgramsAdvanced', window );">Number of programs advanced | Program</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstraZenecaMember', window );">Oncology [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 7,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
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<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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for development milestones 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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for regulatory milestones 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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 minimum amount of payments receivable for license fees and substantive milestones 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_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPotentialPayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 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_NextPotentialPayment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfDrugsThatCanBeLicensedUnderOptionInCollaborationAgreements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 drugs that can be licensed by the partner(s) under their respective collaboration agreements.</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_NumberOfDrugsThatCanBeLicensedUnderOptionInCollaborationAgreements</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_NumberOfObligationsFullySatisified">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 obligations fully satisfied under the collaboration agreement for which revenue is recognized over the period of performance.</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_NumberOfObligationsFullySatisified</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_NumberOfProgramsAdvanced">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 programs advanced 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_NumberOfProgramsAdvanced</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_PaymentsIncludedInTransactionPriceForPerformanceObligation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 payments received since inception of the collaboration agreement included in the transaction price for the performance obligation.</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_PaymentsIncludedInTransactionPriceForPerformanceObligation</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_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 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_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_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_CollaborativeArrangementsAndLicensingAgreementsAstraZenecaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_CollaborativeArrangementsAndLicensingAgreementsAstraZenecaMember</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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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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</table></div>
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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_ConcentrationRiskByBenchmarkAxis=us-gaap_SalesRevenueGoodsNetMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<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_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstraZenecaMember</td>
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<td><strong> Data Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_IONISAZ525Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
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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;">srt_ProductOrServiceAxis=ions_IONISAZ625Member</td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
<td></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstraZenecaMember</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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<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_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember</td>
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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6837218976">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Bayer (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">1 Months Ended</th>
<th class="th" colspan="3">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
</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>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2015 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2017 </div>
<div>USD ($)</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>
<td class="text">&#160;<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">$ 145,395<span></span>
</td>
<td class="nump">$ 118,314<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
<td class="nump">$ 346,387<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 233,362<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>
<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>
<td class="text">&#160;<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">62,639<span></span>
</td>
<td class="nump">$ 83,697<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">225,584<span></span>
</td>
<td class="nump">$ 280,281<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="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>
<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_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones', window );">Maximum amount of payments receivable for license fees and substantive milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">385,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">385,000<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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">125,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">125,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones', window );">Maximum amount of payments receivable for commercialization milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">110,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">110,000<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_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">175,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">175,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NextPotentialMilestonePayment', window );">Next prospective milestone</a></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>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl 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="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 6,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 6,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 9,300<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] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">19.00%<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_CollaborativeArrangementsAndLicensingAgreementsBayerMember', window );">Bayer [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement', window );">Royalty percentage received on gross margins of both drugs combined</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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] | 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>
<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>
<td class="text">&#160;<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">$ 1,900<span></span>
</td>
<td class="nump">$ 400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 3,300<span></span>
</td>
<td class="nump">$ 66,000<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_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_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="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>
</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="text">&#160;<span></span>
</td>
<td class="nump">3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember', window );">Bayer [Member] | IONIS-FXI [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_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">91,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">91,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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] | R&amp;D Services for IONIS-FXI [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_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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] | IONIS-FXI API [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_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="nump">$ 4,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_PaymentReceivedForAdvancingPrograms', window );">Payment received for advancing programs</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="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">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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>
<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] | IONIS-FXI-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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<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_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">64,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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] | R&amp;D Services for IONIS-FXI-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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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">$ 10,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for commercialization milestones 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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for development milestones 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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for license fees and substantive milestones 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_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones</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_PaymentReceivedForAdvancingPrograms">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 payments received during the period for advancing programs 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_PaymentReceivedForAdvancingPrograms</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_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 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_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 royalty percentage received on gross margins of drug(s) under the collaborative 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_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement</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>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_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>
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<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>
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<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>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Janssen Biotech, Inc. (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="4">1 Months Ended</th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1">17 Months Ended</th>
<th class="th" colspan="1"></th>
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<th class="th">
<div>Jan. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Nov. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jul. 31, 2016 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2014 </div>
<div>USD ($) </div>
<div>PerformanceObligation </div>
<div>Program</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Nov. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2017 </div>
<div>USD ($)</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 145,395<span></span>
</td>
<td class="nump">$ 118,314<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
<td class="nump">$ 346,387<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 233,362<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>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">12,746<span></span>
</td>
<td class="nump">1,727<span></span>
</td>
<td class="nump">14,232<span></span>
</td>
<td class="nump">5,639<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 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">62,639<span></span>
</td>
<td class="nump">$ 83,697<span></span>
</td>
<td class="nump">225,584<span></span>
</td>
<td class="nump">$ 280,281<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember', window );">Janssen Biotech, Inc. [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized', window );">Number of programs under which drugs are to be developed and commercialized | Program</a></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">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>
</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">$ 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="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_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones', window );">Minimum amount of payments receivable for license fees and substantive milestones</a></td>
<td class="text">&#160;<span></span>
</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">800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</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">175,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">175,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</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">440,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">440,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones', window );">Maximum amount of payments receivable for commercialization milestones</a></td>
<td class="text">&#160;<span></span>
</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">180,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">180,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">75,000<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>
</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_NextPotentialMilestonePayment', window );">Next prospective milestone</a></td>
<td class="text">&#160;<span></span>
</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">5,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<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="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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember', window );">Janssen Biotech, Inc. [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">3.00%<span></span>
</td>
<td class="nump">2.00%<span></span>
</td>
<td class="nump">5.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember', window );">Janssen Biotech, Inc. [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>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 15,000<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember', window );">Janssen Biotech, Inc. [Member] | IONIS-JBI1-2.5 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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">$ 5,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember', window );">Janssen Biotech, Inc. [Member] | IONIS-JBI2-2.5 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">$ 5,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember', window );">Janssen Biotech, Inc. [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 900<span></span>
</td>
<td class="nump">$ 3,400<span></span>
</td>
<td class="nump">$ 6,600<span></span>
</td>
<td class="nump">$ 18,100<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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for commercialization milestones 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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for development milestones 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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for regulatory milestones 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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 minimum amount of payments receivable for license fees and substantive milestones 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_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones</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_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 programs under which drugs are to be developed and commercialized 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_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized</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_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 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_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_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>
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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>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
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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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_SalesRevenueGoodsNetMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_SalesRevenueGoodsNetMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<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>
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<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>
<td></td>
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<td>na</td>
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<td><strong> Name:</strong></td>
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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6856057888">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Roche (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="4">1 Months Ended</th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Oct. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jan. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2016 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Apr. 30, 2013 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2017 </div>
<div>USD ($)</div>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 145,395<span></span>
</td>
<td class="nump">$ 118,314<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
<td class="nump">$ 346,387<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 233,362<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>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">62,639<span></span>
</td>
<td class="nump">$ 83,697<span></span>
</td>
<td class="nump">225,584<span></span>
</td>
<td class="nump">$ 280,281<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<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_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<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_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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">4.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">2.00%<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,800<span></span>
</td>
<td class="nump">$ 4,500<span></span>
</td>
<td class="nump">$ 5,400<span></span>
</td>
<td class="nump">$ 5,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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 payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 3,000<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="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_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones', window );">Maximum amount of payments receivable for license fees and substantive milestones</a></td>
<td class="text">&#160;<span></span>
</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">365,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">365,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</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">70,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70,000<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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</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">170,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">170,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones', window );">Maximum amount of payments receivable for commercialization milestones</a></td>
<td class="text">&#160;<span></span>
</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">80,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">80,000<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_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped', window );">Maximum amount of payment receivable for each additional drug developed</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">136,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">136,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl 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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">110,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">110,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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="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_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<td class="text">&#160;<span></span>
</td>
<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">$ 45,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember', window );">IONIS-FB-L [Member] | Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones', window );">Maximum amount of payments receivable for license fees and substantive milestones</a></td>
<td class="nump">684,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 20,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_RoyaltyPercentageReceivedOnNetSalesOfDrug', window );">Royalty percentage received on net sales of drug</a></td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for each additional drug developed 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_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped</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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for commercialization milestones 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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for development milestones 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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for license fees and substantive milestones 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_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for regulatory milestones 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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MilestonePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 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>
</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_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_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 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_RoyaltyPercentageReceivedOnNetSalesOfDrug">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>Royalty percentage received on the net sales of a drug by a collaboration partner 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_RoyaltyPercentageReceivedOnNetSalesOfDrug</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>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_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>
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<tr>
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<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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</table></div>
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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, 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>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<td><strong> Name:</strong></td>
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<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember</td>
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<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember">
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<span style="display: none;">v3.10.0.1</span><table class="report" border="0" cellspacing="2" id="idp6852923568">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, GSK (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Mar. 31, 2010 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($) </div>
<div>Drug</div>
</th>
<th class="th">
<div>Sep. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2017 </div>
<div>USD ($)</div>
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<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<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>
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<td class="nump">$ 145,395<span></span>
</td>
<td class="nump">$ 118,314<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
<td class="nump">$ 346,387<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 233,362<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>
<td class="text">&#160;<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>
<td class="text">&#160;<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">62,639<span></span>
</td>
<td class="nump">$ 83,697<span></span>
</td>
<td class="nump">$ 225,584<span></span>
</td>
<td class="nump">$ 280,281<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember', window );">GSK [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_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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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_UpfrontPaymentReceived', window );">Upfront payment received</a></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="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_NumberOfAntisenseDrugsInDevelopment', window );">Number of antisense drugs in development | Drug</a></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>
</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_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones', window );">Maximum amount of payments receivable for license fees and substantive milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">262,000<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 262,000<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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">47,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">47,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">120,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">120,000<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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones', window );">Maximum amount of payments receivable for commercialization milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></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="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember', window );">GSK [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">4.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">4.00%<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember', window );">GSK [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<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="text">&#160;<span></span>
</td>
<td class="nump">$ 162,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 162,000<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember', window );">GSK [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<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="text">&#160;<span></span>
</td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember', window );">GSK [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>
<td class="text">&#160;<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>
<td class="text">&#160;<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">$ 100<span></span>
</td>
<td class="nump">$ 4,600<span></span>
</td>
<td class="nump">$ 1,500<span></span>
</td>
<td class="nump">$ 14,400<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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for commercialization milestones 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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for development milestones 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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for license fees and substantive milestones 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_MaximumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for regulatory milestones 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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_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_NumberOfAntisenseDrugsInDevelopment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 antisense drugs in development designed to reduce the production of viral proteins associated with hepatitis B virus, or HBV, infection 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_NumberOfAntisenseDrugsInDevelopment</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>
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<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 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>
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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>
</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>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
<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>
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<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>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>
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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>
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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>
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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_ConcentrationRiskByBenchmarkAxis=us-gaap_SalesRevenueGoodsNetMember">
<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_ConcentrationRiskByBenchmarkAxis=us-gaap_SalesRevenueGoodsNetMember</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>
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<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Novartis (Details)<br> $ in Thousands, shares in Millions</strong></div></th>
<th class="th" colspan="2">1 Months Ended</th>
<th class="th" colspan="3">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
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<tr>
<th class="th">
<div>Jul. 31, 2017 </div>
<div>USD ($)</div>
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<th class="th">
<div>Jan. 31, 2017 </div>
<div>Drug</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Mar. 31, 2017 </div>
<div>USD ($) </div>
<div>PerformanceObligation </div>
<div>shares</div>
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<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
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<th class="th">
<div>Sep. 30, 2017 </div>
<div>USD ($)</div>
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<div>Dec. 31, 2017 </div>
<div>USD ($)</div>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="nump">$ 0<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">$ 145,395<span></span>
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<td class="nump">$ 118,314<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">407,559<span></span>
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<td class="nump">346,387<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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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="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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</tr>
<tr class="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>
<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">62,639<span></span>
</td>
<td class="nump">$ 83,697<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">225,584<span></span>
</td>
<td class="nump">$ 280,281<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<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_StockIssuedDuringPeriodSharesNewIssues', window );">Shares issued (in shares) | shares</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.6<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="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_ProceedsFromSaleOfCommonStockIncludingPremiumPaid', window );">Proceeds from sale of common stock</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 108,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_PremiumReceivedOnSharesIssued', window );">Premium received on shares issued</a></td>
<td class="text">&#160;<span></span>
</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">28,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture', window );">Potential premium received if common stock is purchased in the future</a></td>
<td class="text">&#160;<span></span>
</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">5,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " 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="text">&#160;<span></span>
</td>
<td class="nump">$ 34,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 34,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 70,700<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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="text">&#160;<span></span>
</td>
<td class="nump">5.00%<span></span>
</td>
<td class="nump">8.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10.00%<span></span>
</td>
<td class="nump">6.00%<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<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_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised', window );">Number of drugs with exclusive option that could be exercised | Drug</a></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>
<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 Services for 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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="text">&#160;<span></span>
</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">64,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member] | Delivery of 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<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_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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 Services for AKCEA-APOCIII-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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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="text">&#160;<span></span>
</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">40,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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] | Delivery of AKCEA-APOCIII-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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<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_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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">$ 7,200<span></span>
</td>
<td class="nump">$ 9,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 42,700<span></span>
</td>
<td class="nump">$ 21,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<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="text">&#160;<span></span>
</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>
</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_PortionOfUpfrontPaymentRetained', window );">Portion of upfront payment retained</a></td>
<td class="text">&#160;<span></span>
</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">60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_PortionOfUpfrontPaymentPaidAsASublicenseFee', window );">Portion of upfront payment paid as a sublicense fee</a></td>
<td class="text">&#160;<span></span>
</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">$ 15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_LicenseFeePaidPerDrug', window );">License fee receivable per drug</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="nump">$ 150,000<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_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee', window );">Percentage of license fees, milestone payments and royalties paid as sublicense fee</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">50.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfPrivatePlacement', window );">Proceeds from sale of common stock to Novartis in a private placement</a></td>
<td class="nump">$ 50,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<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_MaximumAmountOfPaymentsReceivableForMilestones', window );">Maximum amount of payments receivable for milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">600,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 600,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">290,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">290,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones', window );">Maximum amount of payments receivable for commercialization milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">285,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 285,000<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_RoyaltyPercentageReceivedOnSalesOfDrug', window );">Royalty percentage received on sales of drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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] | Novartis [Member] | AKCEA-APOCIII-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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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_MaximumAmountOfPaymentsReceivableForMilestones', window );">Maximum amount of payments receivable for milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">530,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 530,000<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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">240,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">240,000<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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones', window );">Maximum amount of payments receivable for commercialization milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 265,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 265,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnSalesOfDrug', window );">Royalty percentage received on sales of drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</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_LicenseFeePaidPerDrug">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 license fee payment receivable per drug 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_LicenseFeePaidPerDrug</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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for commercialization milestones 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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for development milestones 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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for milestones 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_MaximumAmountOfPaymentsReceivableForMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable for regulatory milestones 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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 drugs with an exclusive option that could be exercised to develop and commercialize the drug and a license fee is paid under the collaboration agreement. The collaboration partner will assume all further global development, regulatory and commercialization activities for the licensed drug.</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_NumberOfDrugsWithExclusiveOptionThatCouldBeExercised</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_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 license fees, milestone payments and royalties paid as sublicense fee 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_PercentageOfLicenseFeesMilestonePaymentsAndRoyaltiesPaidAsSublicenseFee</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>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PortionOfUpfrontPaymentPaidAsASublicenseFee">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 upfront payment received during the period under the collaboration agreement that was paid as a sublicense fee.</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_PortionOfUpfrontPaymentPaidAsASublicenseFee</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_PortionOfUpfrontPaymentRetained">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 upfront payment received during the period under the collaboration agreement that was retained by the entity.</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_PortionOfUpfrontPaymentRetained</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_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 potential premium received if common stock is purchased in the future under a Stock Purchase Agreement (SPA) in conjunction with 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_PotentialPremiumReceivedIfCommonStockIsPurchasedInTheFuture</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_PremiumReceivedOnSharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 premium received over the trading price of common stock at the time of purchase.</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_PremiumReceivedOnSharesIssued</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_ProceedsFromSaleOfCommonStockIncludingPremiumPaid">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 inflow from the sale of common stock, including the premium paid for the purchase of 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_ProceedsFromSaleOfCommonStockIncludingPremiumPaid</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_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 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_RoyaltyPercentageReceivedOnSalesOfDrug">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>Royalty percentage received on the sales of a drug by a collaboration partner 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_RoyaltyPercentageReceivedOnSalesOfDrug</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>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_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>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">$ 145,395<span></span>
</td>
<td class="nump">$ 118,314<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
<td class="nump">$ 346,387<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 233,362<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember', window );">PTC 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="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>
<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">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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">12,000<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">12,000<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember', window );">PTC Therapeutics [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<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">8.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">3.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPTCTherapeuticsMember', window );">PTC Therapeutics [Member] | Sublicense 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_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 7,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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] | PTC 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_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_PaymentReceivableUnderLicenseAgreement', window );">Payment receivable under license agreement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">26,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 26,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromLicenseFeesReceived', window );">Payment received under license agreement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">12,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval', window );">Payment to be received on earlier of FDA or EMA approval of WAYLIVRA</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6,000<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_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones', window );">Maximum amount of payments receivable per drug for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 8,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 8,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner', window );">Royalty percentage received on net sales of each drug in Latin America from PTC</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil', window );">Period before PTC pays royalties on net sales of product after first commercial sale in Brazil</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">12 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties', window );">Minimum revenue recognized in Latin America by PTC before paying royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | PTC Therapeutics [Member] | License Fees [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_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 12,000<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>
</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_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 amount of payments receivable per drug or program for regulatory milestone payments 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_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones</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_PaymentReceivableUnderLicenseAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 payments expected to be received under the license 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_PaymentReceivableUnderLicenseAgreement</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_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 payment receivable under the license agreement to be received on the earlier of approval by the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA) 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_PaymentReceivableUnderLicenseAgreementToBePaidAfterApproval</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_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 before collaboration partner pays royalties on net sales of product after first commercial sale in Brazil, 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_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil</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>
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<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 );">+ 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 );">+ 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>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>
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<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>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Cash received from licensees for license fees during the current 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 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (a)<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">
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<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>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NumberOfReportableSegments', window );">Number of reportable segments | Segment</a></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>
<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>
<td class="text">&#160;<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">$ 145,395<span></span>
</td>
<td class="nump">$ 118,314<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
<td class="nump">$ 346,387<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_OperatingExpenses', window );">Total operating expenses</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">163,967<span></span>
</td>
<td class="nump">107,002<span></span>
</td>
<td class="nump">479,716<span></span>
</td>
<td class="nump">309,140<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="num">(18,572)<span></span>
</td>
<td class="nump">11,312<span></span>
</td>
<td class="num">(72,157)<span></span>
</td>
<td class="nump">37,247<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="nump">2,247,913<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,247,913<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,322,774<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>
<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>
<td class="text">&#160;<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">82,756<span></span>
</td>
<td class="nump">34,617<span></span>
</td>
<td class="nump">181,975<span></span>
</td>
<td class="nump">66,106<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<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>
<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">70,010<span></span>
</td>
<td class="nump">32,890<span></span>
</td>
<td class="nump">167,743<span></span>
</td>
<td class="nump">60,467<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<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>
<td class="text">&#160;<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">12,746<span></span>
</td>
<td class="nump">1,727<span></span>
</td>
<td class="nump">14,232<span></span>
</td>
<td class="nump">5,639<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<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>
<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">$ 62,639<span></span>
</td>
<td class="nump">83,697<span></span>
</td>
<td class="nump">$ 225,584<span></span>
</td>
<td class="nump">280,281<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<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_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>
<td class="text">&#160;<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_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">75.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">75.00%<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="text">&#160;<span></span>
</td>
<td class="nump">68.00%<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_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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 when TEGSEDI received marketing authorization in the U.S. (in shares) | shares</a></td>
<td class="nump">1.7<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
<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">$ 178,061<span></span>
</td>
<td class="nump">108,408<span></span>
</td>
<td class="nump">$ 410,025<span></span>
</td>
<td class="nump">379,082<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_OperatingExpenses', window );">Total operating expenses</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">87,664<span></span>
</td>
<td class="nump">81,019<span></span>
</td>
<td class="nump">279,084<span></span>
</td>
<td class="nump">242,753<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="nump">90,397<span></span>
</td>
<td class="nump">27,389<span></span>
</td>
<td class="nump">130,941<span></span>
</td>
<td class="nump">136,329<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="nump">2,446,425<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,446,425<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,342,578<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>
<td class="text">&#160;<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>
<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">77,956<span></span>
</td>
<td class="nump">34,617<span></span>
</td>
<td class="nump">177,175<span></span>
</td>
<td class="nump">66,106<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<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>
<td class="text">&#160;<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">70,010<span></span>
</td>
<td class="nump">32,890<span></span>
</td>
<td class="nump">167,743<span></span>
</td>
<td class="nump">60,467<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<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>
<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">7,946<span></span>
</td>
<td class="nump">1,727<span></span>
</td>
<td class="nump">9,432<span></span>
</td>
<td class="nump">5,639<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<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>
<td class="text">&#160;<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">100,105<span></span>
</td>
<td class="nump">73,791<span></span>
</td>
<td class="nump">232,850<span></span>
</td>
<td class="nump">312,976<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>
</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>
<td class="text">&#160;<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>
<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">19,241<span></span>
</td>
<td class="nump">9,906<span></span>
</td>
<td class="nump">54,670<span></span>
</td>
<td class="nump">21,712<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_OperatingExpenses', window );">Total operating expenses</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">84,249<span></span>
</td>
<td class="nump">26,013<span></span>
</td>
<td class="nump">213,428<span></span>
</td>
<td class="nump">120,884<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="num">(65,008)<span></span>
</td>
<td class="num">(16,107)<span></span>
</td>
<td class="num">(158,758)<span></span>
</td>
<td class="num">(99,172)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="nump">379,128<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">379,128<span></span>
</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">268,804<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>
<td class="text">&#160;<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>
<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">12,000<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">12,000<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>
<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>
<td class="text">&#160;<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">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<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>
<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">12,000<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">12,000<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>
<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>
<td class="text">&#160;<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">7,241<span></span>
</td>
<td class="nump">9,906<span></span>
</td>
<td class="nump">42,670<span></span>
</td>
<td class="nump">21,712<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<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>
<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="num">(51,907)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(57,136)<span></span>
</td>
<td class="num">(54,407)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_OperatingExpenses', window );">Total operating expenses</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(7,946)<span></span>
</td>
<td class="num">(30)<span></span>
</td>
<td class="num">(12,796)<span></span>
</td>
<td class="num">(54,497)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="num">(43,961)<span></span>
</td>
<td class="nump">30<span></span>
</td>
<td class="num">(44,340)<span></span>
</td>
<td class="nump">90<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="num">(577,641)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(577,641)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (288,608)<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>
<td class="text">&#160;<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>
<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="num">(7,200)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(7,200)<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>
<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>
<td class="text">&#160;<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">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<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>
<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="num">(7,200)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(7,200)<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>
<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>
<td class="text">&#160;<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="num">$ (44,707)<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">$ (49,936)<span></span>
</td>
<td class="num">$ (54,407)<span></span>
</td>
<td class="text">&#160;<span></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 when TEGSEDI received marketing authorization in one or more countries or approval from a government agency, such as the Food and Drug Administration (FDA).</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_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_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>
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<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 );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<td class="text">&#160;<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">72.00%<span></span>
</td>
<td class="nump">74.00%<span></span>
</td>
<td class="nump">58.00%<span></span>
</td>
<td class="nump">57.00%<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_ConcentrationRiskByBenchmarkAxis=us-gaap_SalesRevenueGoodsNetMember', window );">Revenue [Member] | Customer Concentration [Member] | Partner B [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_SignificantPartnersAbstract', window );"><strong>Significant Partners [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_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">10.00%<span></span>
</td>
<td class="nump">4.00%<span></span>
</td>
<td class="nump">21.00%<span></span>
</td>
<td class="nump">4.00%<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_ConcentrationRiskByBenchmarkAxis=us-gaap_SalesRevenueGoodsNetMember', window );">Revenue [Member] | Customer Concentration [Member] | Partner C [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_SignificantPartnersAbstract', window );"><strong>Significant Partners [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="nump">5.00%<span></span>
</td>
<td class="nump">8.00%<span></span>
</td>
<td class="nump">10.00%<span></span>
</td>
<td class="nump">6.00%<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_ConcentrationRiskByBenchmarkAxis=us-gaap_SalesRevenueGoodsNetMember', window );">Revenue [Member] | Customer Concentration [Member] | Partner 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_SignificantPartnersAbstract', window );"><strong>Significant Partners [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_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">8.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">3.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_SalesRevenueGoodsNetMember', window );">Revenue [Member] | Customer Concentration [Member] | Partner E [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_SignificantPartnersAbstract', window );"><strong>Significant Partners [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="nump">1.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">19.00%<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_ConcentrationRiskByBenchmarkAxis=us-gaap_AccountsReceivableMember', window );">Contracts Receivables [Member] | Credit Concentration [Member] | Significant Partners [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_SignificantPartnersAbstract', window );"><strong>Significant Partners [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_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">84.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">84.00%<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_NumberOfSignificantPartners', window );">Number of significant partners</a></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="nump">2<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfSignificantPartners">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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 number of significant partners.</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_NumberOfSignificantPartners</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_SignificantPartnersAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_SignificantPartnersAbstract</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_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_ConcentrationRiskByBenchmarkAxis=us-gaap_SalesRevenueGoodsNetMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_SalesRevenueGoodsNetMember</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>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_MajorCustomersAxis=ions_PartnerAMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_PartnerAMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_MajorCustomersAxis=ions_PartnerBMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_PartnerBMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_MajorCustomersAxis=ions_PartnerCMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_PartnerCMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_MajorCustomersAxis=ions_PartnerDMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_PartnerDMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_MajorCustomersAxis=ions_PartnerEMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_PartnerEMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_AccountsReceivableMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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><strong> Name:</strong></td>
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end
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
