<SUBMISSION>
<ACCESSION-NUMBER>0001104659-05-025551
<TYPE>8-K
<PUBLIC-DOCUMENT-COUNT>4
<PERIOD>20050524
<ITEMS>1.01
<ITEMS>9.01
<FILING-DATE>20050526
<DATE-OF-FILING-DATE-CHANGE>20050526
<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>05859031
</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>a05-9920_18k.htm
<DESCRIPTION>8-K
<TEXT>
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<p style="border:none;margin:0in 0in .0001pt;padding:0in;text-align:justify;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>

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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" 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="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;">May 24, 2005</font></b></font></p>

<p style="margin:0in 0in .0001pt;text-align:justify;"><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="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" style="font-size:10.0pt;">&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;">Delaware</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;">(State or Other
Jurisdiction of Incorporation)</font></p>

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

<div align="center">

<table border="0" cellspacing="0" cellpadding="0" width="80%" style="border-collapse:collapse;width:80.0%;">
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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;">000-19125</font></b></p>
  </td>
  <td width="6%" valign="bottom" style="padding:0in .7pt 0in .7pt;width:6.92%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><b><font size="2" face="Times New Roman" style="font-size:1.0pt;font-weight:bold;">&nbsp;</font></b></p>
  </td>
  <td width="46%" valign="top" style="padding:0in .7pt 0in .7pt;width:46.54%;">
  <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="46%" valign="top" style="padding:0in .7pt 0in .7pt;width:46.54%;">
  <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="6%" valign="bottom" style="padding:0in .7pt 0in .7pt;width:6.92%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="46%" valign="top" style="padding:0in .7pt 0in .7pt;width:46.54%;">
  <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>
</table>

</div>

<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="center" style="font-size:10.0pt;margin:0in 0in .0001pt;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">1896
Rutherford Road<br>
Carlsbad, CA 92008<br>
</font></b>(Address of Principal Executive Offices and Zip Code)</p>

<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>

<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>

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

<table border="0" cellspacing="0" cellpadding="0" width="100%" style="border-collapse:collapse;width:100.0%;">
 <tr>
  <td width="4%" valign="top" style="padding:0in 0in 0in 0in;width:4.0%;">
  <p style="margin:0in 0in .0001pt;text-align:justify;"><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font></p>
  </td>
  <td width="599" valign="top" style="padding:0in 0in 0in 0in;width:449.3pt;">
  <p style="margin:0in 0in .0001pt;text-align:justify;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Written communications pursuant to Rule 425 under
  the Securities Act (17 CFR 230.425) </font></p>
  </td>
 </tr>
</table>

<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;width:100.0%;">
 <tr>
  <td width="4%" valign="top" style="padding:0in 0in 0in 0in;width:4.0%;">
  <p style="margin:0in 0in .0001pt;text-align:justify;"><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font></p>
  </td>
  <td width="599" valign="top" style="padding:0in 0in 0in 0in;width:449.3pt;">
  <p style="margin:0in 0in .0001pt;text-align:justify;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Soliciting material pursuant to Rule 14a-12 under
  the Exchange Act (17 CFR 240.14a-12) </font></p>
  </td>
 </tr>
</table>

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

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 <tr>
  <td width="4%" valign="top" style="padding:0in 0in 0in 0in;width:4.0%;">
  <p style="margin:0in 0in .0001pt;text-align:justify;"><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font></p>
  </td>
  <td width="599" valign="top" style="padding:0in 0in 0in 0in;width:449.3pt;">
  <p style="margin:0in 0in .0001pt;text-align:justify;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Pre-commencement communications pursuant to Rule
  14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) </font></p>
  </td>
 </tr>
</table>

<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;width:100.0%;">
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  <td width="4%" valign="top" style="padding:0in 0in 0in 0in;width:4.0%;">
  <p style="margin:0in 0in .0001pt;text-align:justify;"><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font></p>
  </td>
  <td width="599" valign="top" style="padding:0in 0in 0in 0in;width:449.3pt;">
  <p style="margin:0in 0in .0001pt;text-align:justify;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Pre-commencement communications pursuant to Rule
  13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) </font></p>
  </td>
 </tr>
</table>

<div style="border:none;border-bottom:double windowtext 9.0pt;padding:0in 0in 0in 0in;">

<p style="border:none;margin:0in 0in .0001pt;padding:0in;text-align:justify;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>

</div>

<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>

<div align="left" style="margin:0in 0in .0001pt;text-align:left;"><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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<div style="font-family:Times New Roman;">

<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>

<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;">Item 1.01&#160;&#160;&#160;&#160;&#160;&#160; Entry
into Material Agreements.</font></b></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;">On May 24, 2005, Isis Pharmaceuticals, Inc. (the &#147;Company&#148;) issued a
press release announcing that it</font> has entered into a multi-year drug discovery collaboration with Pfizer
Inc. to identify second-generation antisense drugs for the treatment of
ophthalmic disease.&#160; In addition, the
Company intends to present certain information related to this collaboration at
its upcoming annual meeting of stockholders.</p>

<p style="margin:0in 0in .0001pt;text-align:justify;"><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;">Item 9.01.&#160;&#160;&#160;&#160;&#160; Financial
Statements and Exhibits.</font></b></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;">(c)&#160; Exhibits.</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;">&nbsp;</font></b></p>

<table border="0" cellspacing="0" cellpadding="0" width="90%" style="border-collapse:collapse;margin-left:.5in;width:90.0%;">
 <tr>
  <td width="6%" valign="top" style="padding:0in 0in 0in 0in;width:6.34%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">99.1</font></p>
  </td>
  <td width="3%" valign="bottom" style="padding:0in 0in 0in 0in;width:3.04%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="90%" valign="top" style="padding:0in 0in 0in 0in;width:90.62%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Press Release
  dated May 24, 2005.</font></p>
  </td>
 </tr>
 <tr>
  <td width="6%" valign="top" style="padding:0in 0in 0in 0in;width:6.34%;">
  <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>
  </td>
  <td width="3%" valign="bottom" style="padding:0in 0in 0in 0in;width:3.04%;">
  <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>
  </td>
  <td width="90%" valign="top" style="padding:0in 0in 0in 0in;width:90.62%;">
  <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>
  </td>
 </tr>
 <tr>
  <td width="6%" valign="top" style="padding:0in 0in 0in 0in;width:6.34%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">99.2</font></p>
  </td>
  <td width="3%" valign="bottom" style="padding:0in 0in 0in 0in;width:3.04%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="90%" valign="top" style="padding:0in 0in 0in 0in;width:90.62%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Slide for annual
  meeting of stockholders.</font></p>
  </td>
 </tr>
</table>

<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="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 align="left" style="margin:0in 0in .0001pt;text-align:left;"><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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<div style="font-family:Times New Roman;">

<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>

<p style="font-weight:bold;margin:0in 0in .0001pt;page-break-after:avoid;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-variant:normal !important;text-transform:uppercase;">SIGNATURE</font></b></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;">&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 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;">&nbsp;</font></p>

<table border="0" cellspacing="0" cellpadding="0" width="100%" style="border-collapse:collapse;width:100.0%;">
 <tr>
  <td width="53%" valign="top" style="padding:0in 0in 0in 0in;width:53.92%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="46%" colspan="3" valign="top" style="padding:0in 0in 0in 0in;width:46.08%;">
  <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;text-transform:uppercase;">Isis Pharmaceuticals, Inc.</font></b></p>
  </td>
 </tr>
 <tr>
  <td width="53%" valign="top" style="padding:0in 0in 0in 0in;width:53.92%;">
  <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>
  </td>
  <td width="46%" colspan="3" valign="top" style="padding:0in 0in 0in 0in;width:46.08%;">
  <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;text-transform:uppercase;">&nbsp;</font></b></p>
  </td>
 </tr>
 <tr>
  <td width="53%" valign="top" style="padding:0in 0in 0in 0in;width:53.92%;">
  <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>
  </td>
  <td width="46%" colspan="3" valign="top" style="padding:0in 0in 0in 0in;width:46.08%;">
  <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;text-transform:uppercase;">&nbsp;</font></b></p>
  </td>
 </tr>
 <tr>
  <td width="53%" valign="top" style="padding:0in 0in 0in 0in;width:53.92%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Dated: May 24,
  2005</font></p>
  </td>
  <td width="3%" colspan="2" valign="top" style="padding:0in 0in 0in 0in;width:3.84%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">By:</font></p>
  </td>
  <td width="42%" valign="top" style="border:none;border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;width:42.24%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">/s/ B. Lynne
  Parshall</font></p>
  </td>
 </tr>
 <tr>
  <td width="53%" valign="top" style="padding:0in 0in 0in 0in;width:53.92%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="3%" valign="top" style="padding:0in 0in 0in 0in;width:3.16%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="42%" colspan="2" valign="top" style="border:none;border-top:solid windowtext 1.0pt;padding:0in 0in 0in 0in;width:42.92%;">
  <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;text-transform:uppercase;">B. Lynne Parshall</font></b></p>
  </td>
 </tr>
 <tr>
  <td width="53%" valign="top" style="padding:0in 0in 0in 0in;width:53.92%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="3%" valign="top" style="padding:0in 0in 0in 0in;width:3.16%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="42%" colspan="2" valign="top" style="padding:0in 0in 0in 0in;width:42.92%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Executive Vice
  President,</font></p>
  </td>
 </tr>
 <tr>
  <td width="53%" valign="top" style="padding:0in 0in 0in 0in;width:53.92%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="3%" valign="top" style="padding:0in 0in 0in 0in;width:3.16%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="42%" colspan="2" valign="top" style="padding:0in 0in 0in 0in;width:42.92%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Chief Financial
  Officer and Director</font></p>
  </td>
 </tr>
 <tr height="0">
  <td width="403" style="border:none;"></td>
  <td width="24" style="border:none;"></td>
  <td width="5" style="border:none;"></td>
  <td width="316" style="border:none;"></td>
 </tr>
</table>

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

<p style="margin:0in 0in .0001pt;text-align:justify;"><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:.5in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">INDEX TO EXHIBITS</font></p>

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

<p style="margin:0in 0in .0001pt;text-align:justify;"><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 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:8.5pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Press
Release dated May 24, 2005.</p>

<p align="left" style="margin:0in 0in .0001pt .5in;text-align:left;text-indent:0in;"><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 .5in;text-align:left;text-indent:0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">99.2</font><font size="1" style="font-size:8.5pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Slide for annual
meeting of stockholders.</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;">&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;">3</font></p>

<div align="left" style="margin:0in 0in .0001pt;text-align:left;text-indent:0in;"><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 align="right" style="margin:0in 0in .0001pt .5in;text-align:right;text-indent:-.5in;"><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 3.5in;"><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%;">
 <tr>
  <td width="61%" valign="top" style="padding:0in 0in 0in 0in;width:61.92%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="8%" valign="top" style="padding:0in 0in 0in 0in;width:8.16%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Contact:</font></p>
  </td>
  <td width="19%" valign="top" style="padding:0in 0in 0in 0in;width:19.34%;">
  <p align="right" style="margin:0in 0in .0001pt;text-align:right;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Claudine
  Prowse, Ph.D.</font></p>
  </td>
  <td width="10%" valign="top" style="padding:0in 0in 0in 0in;width:10.58%;">
  <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="61%" valign="top" style="padding:0in 0in 0in 0in;width:61.92%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="8%" valign="bottom" style="padding:0in 0in 0in 0in;width:8.16%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="19%" valign="top" style="padding:0in 0in 0in 0in;width:19.34%;">
  <p align="right" style="margin:0in 0in .0001pt;text-align:right;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Isis
  Pharmaceuticals, Inc.</font></p>
  </td>
  <td width="10%" valign="top" style="padding:0in 0in 0in 0in;width:10.58%;">
  <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="61%" valign="top" style="padding:0in 0in 0in 0in;width:61.92%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="8%" valign="bottom" style="padding:0in 0in 0in 0in;width:8.16%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
  </td>
  <td width="19%" valign="top" style="padding:0in 0in 0in 0in;width:19.34%;">
  <p align="right" style="margin:0in 0in .0001pt;text-align:right;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">760-603-2331&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;</font></p>
  </td>
  <td width="10%" valign="top" style="padding:0in 0in 0in 0in;width:10.58%;">
  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</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">&nbsp;</font></p>

<p align="left" style="margin:0in 0in .0001pt .5in;text-align:left;text-indent:.5in;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">ISIS PHARMACEUTICALS ANNOUNCES
COLLABORATION WITH PFIZER TO DISCOVER ANTISENSE DRUGS FOR THE TREATMENT OF EYE
DISEASE</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;">&nbsp;</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;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">CARLSBAD, CA, May 24, 2005</font></b> &#150; Isis Pharmaceuticals Inc. (NASDAQ: ISIS)
has entered into a multi-year drug discovery collaboration with Pfizer Inc
(NYSE: PFE) to identify second-generation antisense drugs for the treatment of
ophthalmic disease.&#160; Under the terms of
the agreement, Isis will receive a technology access fee of $1 million,
research funding, and milestone payments.&#160;
In addition, Isis will receive royalties on the sale of drugs resulting
from the collaboration.</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;">Using Isis&#146; proprietary second-generation
antisense platform, the companies will work together to identify antisense
drugs against targets selected by Pfizer.&#160;
Pfizer will be responsible for clinical development and
commercialization of the antisense drugs.&#160;
Pfizer may develop the antisense drugs identified in the collaboration
for all human health indications.</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" style="font-size:10.0pt;">&#147;Isis has already shown that antisense drugs
can be effective in treating ocular diseases, having discovered and developed
Vitravene<sup>&#174;</sup>. We are excited to contribute to Pfizer&#146;s leading
ophthalmology program and at the same time work with a recognized expert to
extend the technology beyond our primary therapeutic focus,&#148; said C. Frank
Bennett, Isis&#146; Vice President of Antisense Research.</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" style="font-size:10.0pt;">&#147;This new collaboration reflects our active
strategy to work with recognized leaders such as Pfizer to broaden and deepen
our antisense pipeline moving forward. Because the antisense technology
platform that Isis has pioneered allows us to very rapidly discover highly
selective drugs to almost any gene target, we are able not only to keep our own
pipeline full, but also provide drug candidates to partners,&#148; added Dr.
Bennett.</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="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">ABOUT ISIS
PHARMACEUTICALS, INC.</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="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 11 antisense products in development to treat metabolic, cardiovascular
and inflammatory diseases, and cancer. Through its Ibis division, Isis is
developing a system to identify infectious organisms.&#160; 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 </font>http://www.isispharm.com.</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;">This press release includes
forward-looking statements concerning Isis&#146; collaboration with Pfizer Inc and
the development, therapeutic potential and safety of antisense drugs in
treating</font></p>

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

<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">ophthalmic disease. 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.&#160; 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, in developing and commercializing technology and systems
used to identify infectious agents, and in the endeavor of building a business
around such products and services. 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.&#160; Although our
forward-looking statements reflect the good faith judgment of our management,
these statements can only be based on facts and factors currently known by us.&#160; As a result, you are cautioned not to rely on
these forward-looking statements.&#160; These
and other risks concerning 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, 2004, and quarterly report on Form 10-Q for the quarter
ended March 30, 2005<b><i><font style="font-style:italic;font-weight:bold;">,</font></i></b>
which are on file with the U.S. Securities and Exchange Commission (SEC).&#160; 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 style="font-size:10.0pt;line-height:normal;margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Vitravene</font><font face="Symbol">&#210;</font> is a registered trademark of Novartis AG</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="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;"># # #</font></p>

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

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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 99.2</font></b></p>

<p align="right" style="margin:0in 0in .0001pt;text-align:right;"><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"><img width="720" height="540" src="g99201moimage001.jpg" alt="GRAPHIC"></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;"><i><font size="2" face="Times New Roman" style="font-size:10.0pt;font-style:italic;"><a href="#MultiyearDrugDisc_231651" title="Click to goto Slide 1">Link to searchable text of slide shown above</a></font></i></p>

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

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<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="5" face="Times New Roman" style="font-size:18.0pt;font-weight:bold;">Searchable
text section of graphics shown above</font></b></p>

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

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

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<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="font-family:Times New Roman;font-size:10.0pt;margin:0in 0in .0001pt;text-align:center;"><a name="MultiyearDrugDisc_231651"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Multi-year
Drug Disc</font></b></a><b><font style="font-weight:bold;">overy and Development<br>
Collaboration with Pfizer</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;">Creating Second-generation Antisense Drugs for Ocular Diseases</font></b></p>

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

<p style="font-family:Times New Roman;font-size:10.0pt;margin:0in 0in .0001pt;"><b><font size="3" face="Times New Roman" style="font-size:12.0pt;font-weight:bold;">&#149;</font></b><b><font size="1" style="font-size:8.5pt;font-weight:bold;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Work
with recognized expert to extend the technology beyond Isis&#146; primary
therapeutic focus</b></p>

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

<p style="font-family:Times New Roman;font-size:10.0pt;margin:0in 0in .0001pt;"><b><font size="3" face="Times New Roman" style="font-size:12.0pt;font-weight:bold;">&#149;</font></b><b><font size="1" style="font-size:8.5pt;font-weight:bold;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Expand
the application of oligonucleotide drugs for treatment ocular diseases</b></p>

<p style="font-family:Times New Roman;font-size:10.0pt;margin:0in 0in .0001pt .5in;"><b><font size="3" face="Times New Roman" style="font-size:12.0pt;font-weight:bold;">&#149;</font></b><b><font size="1" style="font-size:8.5pt;font-weight:bold;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Vitravene
&#153;</b></p>

<p style="font-family:Times New Roman;font-size:10.0pt;margin:0in 0in .0001pt .5in;"><b><font size="3" face="Times New Roman" style="font-size:12.0pt;font-weight:bold;">&#149;</font></b><b><font size="1" style="font-size:8.5pt;font-weight:bold;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Macugen</b><b><sup><font style="font-weight:bold;"> &#174;</font></sup></b></p>

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

<p style="font-family:Times New Roman;font-size:10.0pt;margin:0in 0in .0001pt;"><b><font size="3" face="Times New Roman" style="font-size:12.0pt;font-weight:bold;">&#149;</font></b><b><font size="1" style="font-size:8.5pt;font-weight:bold;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Payments
to Isis</b></p>

<p style="font-family:Times New Roman;font-size:10.0pt;margin:0in 0in .0001pt 1.0in;text-indent:-.5in;"><b><font size="3" face="Times New Roman" style="font-size:12.0pt;font-weight:bold;">&#149;</font></b><b><font size="1" style="font-size:8.5pt;font-weight:bold;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Technology
access fee, support and milestones for research</b></p>

<p style="font-family:Times New Roman;font-size:10.0pt;margin:0in 0in .0001pt 1.0in;text-indent:-.5in;"><b><font size="3" face="Times New Roman" style="font-size:12.0pt;font-weight:bold;">&#149;</font></b><b><font size="1" style="font-size:8.5pt;font-weight:bold;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Up
to $80 million in development and sales milestones for three successful drugs
in ocular indications</b></p>

<p style="font-family:Times New Roman;font-size:10.0pt;margin:0in 0in .0001pt 1.0in;text-indent:-.5in;"><b><font size="3" face="Times New Roman" style="font-size:12.0pt;font-weight:bold;">&#149;</font></b><b><font size="1" style="font-size:8.5pt;font-weight:bold;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Additional
milestones for other indications</b></p>

<p style="font-family:Times New Roman;font-size:10.0pt;margin:0in 0in .0001pt 1.0in;text-indent:-.5in;"><b><font size="3" face="Times New Roman" style="font-size:12.0pt;font-weight:bold;">&#149;</font></b><b><font size="1" style="font-size:8.5pt;font-weight:bold;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Royalties</b></p>

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

<p style="font-family:Times New Roman;font-size:10.0pt;margin:0in 0in .0001pt;"><b><font size="3" face="Times New Roman" style="font-size:12.0pt;font-weight:bold;">&#149;</font></b><b><font size="1" style="font-size:8.5pt;font-weight:bold;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Pfizer
will develop and commercialize drugs from the collaboration</b></p>

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

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

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end
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</SUBMISSION>
