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  <p align="center" style="border:none;margin:0in 0in .0001pt;padding:0in;text-align:center;text-indent:0in;"><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&nbsp;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)&nbsp;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>April&nbsp;25, 2008</b></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;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>
  
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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="2%" valign="bottom" style="padding:0in 0in 0in 0in;width:2.0%;">
    <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="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 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="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>
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  <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;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">1896 Rutherford Road</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;">Carlsbad,
  CA 92008</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;">(Address of
  Principal Executive Offices and Zip Code)</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;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Registrant&#146;s telephone number, including area
  code: <b>(760) 931-9200</b></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 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&nbsp;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>
  
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font><font size="2" style="font-size:10.0pt;">&#160;&#160;&#160;&#160;&#160; </font><font size="2" style="font-size:10.0pt;">Written communications pursuant to Rule&nbsp;425 under
  the Securities Act (17 CFR 230.425)</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;"><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font><font size="2" style="font-size:10.0pt;">&#160;&#160;&#160;&#160;&#160; </font><font size="2" style="font-size:10.0pt;">Soliciting material pursuant to Rule&nbsp;14a-12 under
  the Exchange Act (17 CFR 240.14a-12)</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;"><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font><font size="2" style="font-size:10.0pt;">&#160;&#160;&#160;&#160;&#160; </font><font size="2" style="font-size:10.0pt;">Pre-commencement communications pursuant to Rule&nbsp;14d-2(b)&nbsp;under
  the Exchange Act (17 CFR 240.14d-2(b))</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;"><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font><font size="2" style="font-size:10.0pt;">&#160;&#160;&#160;&#160;&#160; </font><font size="2" style="font-size:10.0pt;">Pre-commencement communications pursuant to Rule&nbsp;13e-4(c)&nbsp;under
  the Exchange Act (17 CFR 240.13e-4(c))</font></p>
  
  <div style="border:none;border-bottom:double windowtext 6.0pt;padding:0in 0in 0in 0in;">
  
  <p align="left" style="border:none;margin:0in 0in .0001pt;padding:0in;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
  
  </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>
  
  <div align="left" style="margin:0in 0in .0001pt;text-align:left;"><hr size="3" width="100%" noshade color="#010101" align="left"></div>
  
  </div>
  <!-- SEQ.=1,FOLIO='',FILE='C:\JMS\brosent\08-12569-1\task2891997\12569-1-ba.htm',USER='brosent',CD='Apr 24 21:48 2008' -->
  
  
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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 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 8.01.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Other Events.</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;text-indent:.5in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">On April&nbsp;25,
  2008, Isis Pharmaceuticals,&nbsp;Inc. and Genzyme Corp. announced today that
  the FDA has provided guidance regarding approval requirements for mipomersen.&#160; A copy of the Press Release related to the
  guidance is attached hereto as Exhibit&nbsp;99.1 and is incorporated herein by
  reference.</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;">Item 9.01.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#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;">(d)&nbsp; 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>
  
  <table border="0" cellspacing="0" cellpadding="0" width="100%" style="border-collapse:collapse;width:100.0%;">
   <tr>
    <td width="11%" valign="top" style="padding:0in 0in 0in 0in;width:11.66%;">
    <p align="center" style="margin:0in 0in .0001pt 10.0pt;text-align:center;text-indent:-10.0pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">99.1</font></p>
    </td>
    <td width="4%" valign="bottom" style="padding:0in 0in 0in 0in;width:4.34%;">
    <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="84%" valign="top" style="padding:0in 0in 0in 0in;width:84.0%;">
    <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 April&nbsp;25, 2008.</font></p>
    </td>
   </tr>
  </table>
  
  <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;">2</font></p>
  
  <div align="left" style="margin:0in 0in .0001pt;text-align:left;"><hr size="3" width="100%" noshade color="#010101" align="left"></div>
  
  </div>
  <!-- SEQ.=1,FOLIO='2',FILE='C:\JMS\brosent\08-12569-1\task2891997\12569-1-ba.htm',USER='brosent',CD='Apr 24 21:48 2008' -->
  
  
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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="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;">SIGNATURE</font></b></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;">&nbsp;</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;">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="51%" valign="top" style="padding:0in 0in 0in 0in;width:51.0%;">
    <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="49%" colspan="3" valign="top" style="padding:0in 0in 0in 0in;width:49.0%;">
    <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;">ISIS PHARMACEUTICALS, INC.</font></b></p>
    </td>
   </tr>
   <tr>
    <td width="51%" valign="top" style="padding:0in 0in 0in 0in;width:51.0%;">
    <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>
    </td>
    <td width="49%" colspan="3" valign="top" style="padding:0in 0in 0in 0in;width:49.0%;">
    <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="51%" valign="top" style="padding:0in 0in 0in 0in;width:51.0%;">
    <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>
    </td>
    <td width="49%" colspan="3" valign="top" style="padding:0in 0in 0in 0in;width:49.0%;">
    <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="51%" valign="top" style="padding:0in 0in 0in 0in;width:51.0%;">
    <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Dated:
    April&nbsp;25, 2008</font></p>
    </td>
    <td width="3%" colspan="2" valign="top" style="padding:0in 0in 0in 0in;width:3.76%;">
    <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="45%" valign="top" style="border:none;border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;width:45.26%;">
    <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="51%" valign="top" style="padding:0in 0in 0in 0in;width:51.0%;">
    <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:3.42%;">
    <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="45%" colspan="2" valign="top" style="padding:0in 0in 0in 0in;width:45.58%;">
    <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;">B.
    LYNNE PARSHALL</font></b></p>
    </td>
   </tr>
   <tr>
    <td width="51%" valign="top" style="padding:0in 0in 0in 0in;width:51.0%;">
    <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:3.42%;">
    <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="45%" colspan="2" valign="top" style="padding:0in 0in 0in 0in;width:45.58%;">
    <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Chief Operating
    Officer,</font></p>
    </td>
   </tr>
   <tr>
    <td width="51%" valign="top" style="padding:0in 0in 0in 0in;width:51.0%;">
    <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:3.42%;">
    <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="45%" colspan="2" valign="top" style="padding:0in 0in 0in 0in;width:45.58%;">
    <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="381" style="border:none;"></td>
    <td width="26" style="border:none;"></td>
    <td width="3" style="border:none;"></td>
    <td width="338" style="border:none;"></td>
   </tr>
  </table>
  
  <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;">3</font></p>
  
  <div align="left" style="margin:0in 0in .0001pt;text-align:left;"><hr size="3" width="100%" noshade color="#010101" align="left"></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 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 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="9%" valign="top" style="padding:0in 0in 0in 0in;width:9.0%;">
    <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="2%" valign="bottom" style="padding:0in 0in 0in 0in;width:2.26%;">
    <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>
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    <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 April&nbsp;25, 2008.</font></p>
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metadata_filer: {"company-data": {"conformed-name": "ISIS PHARMACEUTICALS INC", "cik": "0000874015", "assigned-sic": "2834", "irs-number": "330336973", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "8-K", "act": "34", "file-number": "000-19125", "film-number": "08775971"}, "business-address": {"street1": "1896 RUTHERFORD ROAD", "city": "CARLSBAD", "state": "CA", "zip": "92008", "phone": "7609319200"}, "mail-address": {"street1": "1896 RUTHERFORD ROAD", "city": "CARLSBAD", "state": "CA", "zip": "92008"}}
text: SECURITIES
  AND EXCHANGE COMMISSION
  Washington,
  D.C.  20549
  FORM 8-K
  CURRENT
  REPORT
  PURSUANT TO SECTION 13 OR 15(d) OF THE
  SECURITIES EXCHANGE ACT OF 1934
  Date of report
  (Date of earliest event reported):
  April 25, 2008
  ISIS PHARMACEUTICALS, INC.
  (Exact Name of
  Registrant as Specified in Charter)
  Delaware
  (State or Other
  Jurisdiction of Incorporation)
  000-19125
  33-0336973
  (Commission File
    No.)
  (IRS Employer
    Identification No.)
  1896 Rutherford Road
  Carlsbad,
  CA 92008
  (Address of
  Principal Executive Offices and Zip Code)
  Registrant's telephone number, including area
  code:
  (760) 931-9200
  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:
  o
  Written communications pursuant to Rule 425 under
  the Securities Act (17 CFR 230.425)
  o
  Soliciting material pursuant to Rule 14a-12 under
  the Exchange Act (17 CFR 240.14a-12)
  o
  Pre-commencement communications pursuant to Rule 14d-2(b) under
  the Exchange Act (17 CFR 240.14d-2(b))
  o
  Pre-commencement communications pursuant to Rule 13e-4(c) under
  the Exchange Act (17 CFR 240.13e-4(c))
  Item 8.01.              Other Events.
  On April 25,
  2008, Isis Pharmaceuticals, Inc. and Genzyme Corp. announced today that
  the FDA has provided guidance regarding approval requirements for mipomersen.  A copy of the Press Release related to the
  guidance is attached hereto as Exhibit 99.1 and is incorporated herein by
  reference.
  Item 9.01.              Financial Statements and Exhibits.
  (d)  Exhibits.
  99.1
  Press Release
    dated April 25, 2008.
  2
  SIGNATURE
  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.
  ISIS PHARMACEUTICALS, INC.
  Dated:
    April 25, 2008
  By:
  /s/ B. Lynne
    Parshall
  B.
    LYNNE PARSHALL
  Chief Operating
    Officer,
  Chief Financial
    Officer and Director
  3
  INDEX TO EXHIBITS
  99.1
  Press Release
    dated April 25, 2008.
  4