<SUBMISSION>
<ACCESSION-NUMBER>0001104659-05-006242
<TYPE>8-K
<PUBLIC-DOCUMENT-COUNT>2
<PERIOD>20050214
<ITEMS>1.01
<ITEMS>9.01
<FILING-DATE>20050214
<DATE-OF-FILING-DATE-CHANGE>20050214
<FILER>
<COMPANY-DATA>
<CONFORMED-NAME>ISIS PHARMACEUTICALS INC
<CIK>0000874015
<ASSIGNED-SIC>2834
<IRS-NUMBER>330336973
<STATE-OF-INCORPORATION>DE
<FISCAL-YEAR-END>1231
</COMPANY-DATA>
<FILING-VALUES>
<FORM-TYPE>8-K
<ACT>34
<FILE-NUMBER>000-19125
<FILM-NUMBER>05607611
</FILING-VALUES>
<BUSINESS-ADDRESS>
<STREET1>2292 FARADAY AVE
<CITY>CARLSBAD
<STATE>CA
<ZIP>92008
<PHONE>7609319200
</BUSINESS-ADDRESS>
<MAIL-ADDRESS>
<STREET1>2292 FARADAY AVE
<CITY>CARLSBAD
<STATE>CA
<ZIP>92008
</MAIL-ADDRESS>
</FILER>
<DOCUMENT>
<TYPE>8-K
<SEQUENCE>1
<FILENAME>a05-3231_18k.htm
<DESCRIPTION>8-K
<TEXT>
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<p align="center" style="margin:0in 0in .0001pt;text-align:center;text-indent:0in;"><b><font size="5" face="Times New Roman" style="font-size:18.0pt;font-weight:bold;">SECURITIES AND EXCHANGE
COMMISSION</font></b></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Washington, D.C.&#160; 20549</font></b></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;text-indent:0in;"><b><font size="5" face="Times New Roman" style="font-size:18.0pt;font-weight:bold;">FORM 8-K</font></b></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;text-indent:0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;text-indent:0in;"><b><font size="3" face="Times New Roman" style="font-size:12.0pt;font-weight:bold;">CURRENT REPORT<br>
PURSUANT TO SECTION&nbsp;13 OR 15(d) OF THE<br>
SECURITIES EXCHANGE ACT OF 1934</font></b></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;text-indent:0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Date of report (Date of earliest event
reported):&#160; <b><font style="font-weight:bold;">February 14,
2005</font></b></font></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;text-indent:0in;"><b><font size="5" face="Times New Roman" style="font-size:18.0pt;font-weight:bold;">ISIS PHARMACEUTICALS, INC.</font></b></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(Exact Name of Registrant as Specified in
Charter)</font></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<table border="0" cellspacing="0" cellpadding="0" width="100%" style="border-collapse:collapse;width:100.0%;">
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  <td width="100%" colspan="3" valign="top" style="padding:0in 0in 0in 0in;width:100.0%;">
  <p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Delaware</font></b></p>
  </td>
 </tr>
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  <td width="100%" colspan="3" valign="top" style="padding:0in 0in 0in 0in;width:100.0%;">
  <p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(State or Other Jurisdiction of
  Incorporation)</font></p>
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  <p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">&nbsp;</font></b></p>
  </td>
  <td width="2%" valign="bottom" style="padding:0in 0in 0in 0in;width:2.0%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
  </td>
  <td width="49%" valign="top" style="padding:0in 0in 0in 0in;width:49.0%;">
  <p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
  </td>
 </tr>
 <tr>
  <td width="49%" valign="top" style="padding:0in 0in 0in 0in;width:49.0%;">
  <p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">000-19125</font></b></p>
  </td>
  <td width="2%" valign="bottom" style="padding:0in 0in 0in 0in;width:2.0%;">
  <p style="margin:0in 0in .0001pt;"><b><font size="2" face="Times New Roman" style="font-size:1.0pt;font-weight:bold;">&nbsp;</font></b></p>
  </td>
  <td width="49%" valign="top" style="padding:0in 0in 0in 0in;width:49.0%;">
  <p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">33-0336973</font></b></p>
  </td>
 </tr>
 <tr>
  <td width="49%" valign="top" style="padding:0in 0in 0in 0in;width:49.0%;">
  <p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(Commission File No.)</font></p>
  </td>
  <td width="2%" valign="bottom" style="padding:0in 0in 0in 0in;width:2.0%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="49%" valign="top" style="padding:0in 0in 0in 0in;width:49.0%;">
  <p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(IRS Employer Identification No.)</font></p>
  </td>
 </tr>
 <tr>
  <td width="49%" valign="top" style="padding:0in 0in 0in 0in;width:49.0%;">
  <p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
  </td>
  <td width="2%" valign="bottom" style="padding:0in 0in 0in 0in;width:2.0%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
  </td>
  <td width="49%" valign="top" style="padding:0in 0in 0in 0in;width:49.0%;">
  <p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
  </td>
 </tr>
 <tr>
  <td width="100%" colspan="3" valign="top" style="padding:0in 0in 0in 0in;width:100.0%;">
  <p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">2292 Faraday Avenue<br>
  Carlsbad, CA 92008</font></b></p>
  </td>
 </tr>
 <tr>
  <td width="100%" colspan="3" valign="top" style="padding:0in 0in 0in 0in;width:100.0%;">
  <p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(Address of Principal Executive Offices and
  Zip Code)</font></p>
  </td>
 </tr>
 <tr>
  <td width="100%" colspan="3" valign="top" style="padding:0in 0in 0in 0in;width:100.0%;">
  <p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
  </td>
 </tr>
 <tr>
  <td width="100%" colspan="3" valign="top" style="padding:0in 0in 0in 0in;width:100.0%;">
  <p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Registrant&#146;s telephone number, including
  area code: <b><font style="font-weight:bold;">(760) 931-9200</font></b></font></p>
  </td>
 </tr>
</table>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Check the appropriate box below
if the Form 8-K filing is intended to simultaneously satisfy the filing
obligation of the registrant under any of the following provisions:</font></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p style="font-size:10.0pt;margin:0in 0in .0001pt;"><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font>&#160;&#160;&#160; Written communications pursuant to Rule 425 under the Securities
Act (17 CFR 230.425) </p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p style="font-size:10.0pt;margin:0in 0in .0001pt;"><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font>&#160;&#160;&#160; Soliciting material pursuant to Rule 14a-12 under the Exchange
Act (17 CFR 240.14a-12) </p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p style="font-size:10.0pt;margin:0in 0in .0001pt;"><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font>&#160;&#160;&#160; Pre-commencement communications pursuant to Rule 14d-2(b) under
the Exchange Act (17 CFR 240.14d-2(b)) </p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p style="font-size:10.0pt;margin:0in 0in .0001pt;"><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font>&#160;&#160;&#160; Pre-commencement communications pursuant to Rule 13e-4(c) under
the Exchange Act (17 CFR 240.13e-4(c)) </p>

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<p style="border:none;margin:0in 0in .0001pt;padding:0in;"><font size="2" face="Times New Roman">&nbsp;</font></p>

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<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

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<hr size="2" width="100%" noshade color="gray" align="left">

</font></div>

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<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p style="margin:0in 0in .0001pt;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Item 1.01&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Entry
into a Material Agreement.</font></b></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p align="left" style="font-size:10.0pt;margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">On February 14, 2005,
Isis Pharmaceuticals, Inc. (the &#147;Company&#148;) issued a press release announcing
that it</font> has licensed an
anti-cancer antisense drug to and Sarissa, Inc., a biotechnology company
emerging from the University of Western Ontario.&#160; The drug is an antisense inhibitor of
thymidylate synthase (TS), a well-known drug target that protects cancer cells
from the effects of several chemotherapy treatments.</p>

<p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>

<p style="margin:0in 0in .0001pt;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Item 9.01.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Financial
Statements and Exhibits.</font></b></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(c)&#160; Exhibits.</font></p>

<p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>

<table border="0" cellspacing="0" cellpadding="0" width="103%" style="border-collapse:collapse;width:103.34%;">
 <tr>
  <td width="103" valign="top" style="padding:0in 0in 0in 0in;width:77.4pt;">
  <p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">99.1</font></p>
  </td>
  <td width="641" valign="top" style="padding:0in 0in 0in 0in;width:480.65pt;">
  <p style="margin:0in 0in .0001pt;text-align:justify;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Press Release dated February 14, 2005.</font></p>
  </td>
 </tr>
</table>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">2</font></p>

<div style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">

<hr size="2" width="100%" noshade color="gray" align="left">

</font></div>

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<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">SIGNATURE</font></b></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p align="left" style="margin:0in 0in .0001pt;text-align:left;text-indent:.5in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Pursuant to the requirements of the Securities Exchange Act of 1934, as
amended, the registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.</font></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<table border="0" cellspacing="0" cellpadding="0" width="100%" style="border-collapse:collapse;margin-left:.7pt;width:100.0%;">
 <tr>
  <td width="52%" valign="top" style="padding:0in .7pt 0in .7pt;width:52.54%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="47%" colspan="3" valign="top" style="padding:0in .7pt 0in .7pt;width:47.46%;">
  <p style="margin:0in 0in .0001pt;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;text-transform:uppercase;">Isis Pharmaceuticals, Inc.</font></b></p>
  </td>
 </tr>
 <tr>
  <td width="52%" valign="top" style="padding:0in .7pt 0in .7pt;width:52.54%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
  </td>
  <td width="47%" colspan="3" valign="top" style="padding:0in .7pt 0in .7pt;width:47.46%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
  </td>
 </tr>
 <tr>
  <td width="52%" valign="top" style="padding:0in .7pt 0in .7pt;width:52.54%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
  </td>
  <td width="47%" colspan="3" valign="top" style="padding:0in .7pt 0in .7pt;width:47.46%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
  </td>
 </tr>
 <tr>
  <td width="52%" valign="top" style="padding:0in .7pt 0in .7pt;width:52.54%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Dated: February 10, 2005</font></p>
  </td>
  <td width="3%" valign="top" style="padding:0in .7pt 0in .7pt;width:3.82%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">By: </font></p>
  </td>
  <td width="41%" valign="top" style="border:none;border-bottom:solid windowtext 1.0pt;padding:0in .7pt 0in .7pt;width:41.32%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">/s/ B. Lynne Parshall</font></p>
  </td>
  <td width="2%" valign="top" style="padding:0in .7pt 0in .7pt;width:2.32%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
 </tr>
 <tr>
  <td width="52%" valign="top" style="padding:0in .7pt 0in .7pt;width:52.54%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="3%" valign="top" style="padding:0in .7pt 0in .7pt;width:3.82%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="43%" colspan="2" valign="top" style="padding:0in .7pt 0in .7pt;width:43.64%;">
  <p style="margin:0in 0in .0001pt;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;text-transform:uppercase;">B. Lynne Parshall</font></b></p>
  </td>
 </tr>
 <tr>
  <td width="52%" valign="top" style="padding:0in .7pt 0in .7pt;width:52.54%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="3%" valign="top" style="padding:0in .7pt 0in .7pt;width:3.82%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="43%" colspan="2" valign="top" style="padding:0in .7pt 0in .7pt;width:43.64%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Executive Vice President,</font></p>
  </td>
 </tr>
 <tr>
  <td width="52%" valign="top" style="padding:0in .7pt 0in .7pt;width:52.54%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="3%" valign="top" style="padding:0in .7pt 0in .7pt;width:3.82%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="43%" colspan="2" valign="top" style="padding:0in .7pt 0in .7pt;width:43.64%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Chief Financial Officer and Director</font></p>
  </td>
 </tr>
</table>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">3</font></p>

<div style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">

<hr size="2" width="100%" noshade color="gray" align="left">

</font></div>

</div>
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<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;text-indent:0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">INDEX TO EXHIBITS</font></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p align="left" style="font-size:10.0pt;margin:0in 0in .0001pt 1.5in;text-align:left;text-indent:-1.0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">99.1</font><font size="1" style="font-size:3.0pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Press
Release dated February 14, 2005.</p>

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<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">4</font></p>

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<p align="right" style="margin:0in 0in .0001pt;text-align:right;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Exhibit 99.1</font></b></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">ISIS PHARMACEUTICALS LICENSES ANTISENSE</font></b></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">ANTI-CANCER DRUG TO SARISSA</font></b></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p style="font-size:10.0pt;margin:0in 0in .0001pt;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">London,
Ontario, Canada and Carlsbad, CA, USA, February 14, 2005</font></b>-
Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) and Sarissa, Inc., a biotechnology
company emerging from the University of Western Ontario, announced today that
Isis has licensed an anti-cancer antisense drug to Sarissa.&#160; The drug is an antisense inhibitor of
thymidylate synthase (TS), a well-known drug target that protects cancer cells
from the effects of several chemotherapy treatments. In preclinical studies,
antisense inhibition of TS suppressed human tumor cell growth and overcame
tumor cell resistance to marketed TS-targeted drugs.</p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&#147;This licensing agreement with
Isis will enable us to move our oncology drug discovery and development program
forward.&#160; The combination of our
knowledge of the biological role of thymidylate synthase with Isis&#146; expertise
in antisense discovery and development and second-generation chemistry has the
potential to yield an exciting and cutting-edge treatment for cancer,&#148; said
Mark Vincent M.D., President and CEO of Sarissa.&#160; &#147;Looking ahead, we plan to complete a series
of preclinical experiments to prepare the drug for IND submission and human
clinical trials.&#148;</font></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&#147;This
transaction with Sarissa is another example of our successful satellite company
partnering program.&#160; Through these
relationships, we are expanding the reach and potential of antisense
therapeutics and participating in the success of multiple companies and
products,&#148; said Nicholas Dean, Ph.D., Vice President of Functional Genomics at
Isis Pharmaceuticals.&#160; &#147;This licensing
agreement will allow us to benefit from Sarissa&#146;s expertise and highly focused
research efforts in cancer, while Sarissa will benefit from our experience in RNA-based
drug discovery and development and access to our intellectual property.&#148;</font></p>

<p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>

<p style="font-size:10.0pt;margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Under the terms of the agreement, </font>Sarissa will pay Isis a $1 million upfront
fee in exchange for the
exclusive, worldwide license to the TS antisense drug.&#160; The upfront fee will be paid with a debt
instrument which will convert into Sarissa stock upon its successful completion
of a venture capital financing. Sarissa will also pay Isis milestone payments
for key clinical and regulatory achievements and royalties on product sales.
Sarissa will be solely
responsible for preclinical and clinical development of the drug.</p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p style="font-size:10.0pt;margin:0in 0in .0001pt;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">About </font></b><b><font style="font-weight:bold;">Thymidylate Synthase (</font>TS)</b></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">TS is an important target in a
wide variety of cancers, including colorectal, breast, stomach, esophageal,
head and neck cancers, and mesothelioma; it is of increasing importance in
non-small cell lung cancer.&#160; In addition
to interfering with the effectiveness of chemotherapy, the TS gene may also
participate in causing cancer. TS is a target for several chemotherapy agents,
including 5-fluorouracil (5-FU), pemetrexed (Alimta&#174;), and raltitrexed
(Tomudex&#174;).</font></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

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<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p style="margin:0in 0in .0001pt;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">About
Sarissa, Inc.</font></b></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Sarissa, Inc. was founded by
Chief Executive Officer, Mark Vincent, M.D., a medical oncologist and Chief
Scientific Officer, James Koropatnick, Ph.D., a cancer research scientist. It
has a focus on the antisense down-regulation of thymidylate synthase as a means
of chemotherapy potentiation.&#160; The
Company plans now to leverage its oncology expertise to develop antisense oligonucleotides
in the clinic.</font></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>

<p style="margin:0in 0in .0001pt;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">About Isis&#146; Anti-Cancer Drug Discovery and Development Partnerships</font></b></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Through both
strategic partnerships and internal research and development programs, Isis has
several ongoing programs focused on identifying antisense drugs for the
treatment of a variety of cancers. Isis&#146; collaboration with Eli Lilly and
Company has resulted in two drugs in development that target cancer. LY2181308
is an anti-cancer drug that targets survivin and LY2275796 is an anti-cancer
drug that targets eIF-4E. Additionally, with Isis&#146; assistance, OncoGenex
Technologies is developing OGX-011, an anti-cancer drug that targets a protein
called clusterin and OGX-225, a cancer drug that targets both Insulin-like
Growth Factor Binding Protein-2 (IGFBP-2) and Insulin-like Growth Factor
Binding Protein-5 (IGFBP-5). IGFBP-2 and IGFBP-5 are genes involved in
regulating growth signals that result in tumor cell growth and the development
of metastatic cancer in hormone-regulated tumors such as prostate and breast
cancers. Isis is also working with Ercole Biotech on the preclinical
development of a Bcl-x antisense drug.&#160;
This drug inhibits the production of splice variants of the Bcl-x gene;
a gene involved in the regulation of apoptosis, or programmed cell death. Internally,
Isis continues its drug discovery efforts in oncology with ISIS 345794, a
second-generation antisense drug that targets STAT-3. This protein is known to
be an important transcription factor that turns on genes required for the
division, growth and death of cells. In addition, Isis has several internal and
partnered research and development programs to treat metabolic, cardiovascular
and inflammatory diseases.</font></p>

<p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>

<p align="left" style="margin:0in 0in .0001pt;text-align:left;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">About Isis Pharmaceuticals, Inc.</font></b></p>

<p align="left" style="font-size:10.0pt;margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Isis Pharmaceuticals,
Inc. is exploiting its expertise in RNA to discover and develop novel human
therapeutic drugs for its pipeline and for its partners. The Company has
successfully commercialized the world&#146;s first antisense drug and has 10
antisense products in development to treat metabolic, cardiovascular and
inflammatory diseases, and cancer. Through its Ibis Therapeutics</font>&#174; program, Isis is developing a
biosensor to identify infectious organisms, and is discovering small molecule
drugs that bind to RNA. As an innovator in RNA-based drug discovery and
development, Isis is the owner or exclusive licensee of more than 1,500 issued
patents worldwide. Additional information about Isis is available at http://www.isispharm.com.</p>

<p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">This press
release includes forward-looking statements regarding Isis Pharmaceuticals and
Sarissa&#146;s licensing agreement and the development, therapeutic potential and
safety of an antisense drug targeting TS for the treatment of cancer.&#160; Any statement describing our goals,
expectations, intentions or beliefs is a forward-looking statement and should
be considered an at-risk statement, including those statements that are
described as Isis&#146; clinical goals. Such statements are subject to certain risks
and uncertainties, particularly those inherent in the process of developing
technology, in discovering and commercializing drugs that are safe and
effective for use as human therapeutics, and in the endeavor of building a
business around such products. Actual results could differ materially from
those discussed in this press release. As a result, you are cautioned not to
rely on these forward-looking statements. These and other risks concerning</font></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

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<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Isis&#146; research
and development programs are described in additional detail in Isis&#146; Annual
Report on Form 10-K for the year ended December 31, 2003, and quarterly report
on Form 10-Q for the quarter ended September 30, 2004, which are on file with
the U.S. Securities and Exchange Commission. Copies of these and other
documents are available from the company.</font></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p align="left" style="font-size:10.0pt;margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Ibis Therapeutics</font>&#174; is a registered trademark of Isis
Pharmaceuticals, Inc.</p>

<p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>

<p align="left" style="font-size:10.0pt;margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Alimta</font>&#174; is a registered trademark of Eli Lilly and
Company.</p>

<p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>

<p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Tomudex&#174;
is a registered trademark of AstraZeneca.</font></p>

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman">&nbsp;</font></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;"># # #</font></p>

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