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<FILING-DATE>20050805
<DATE-OF-FILING-DATE-CHANGE>20050805
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<CONFORMED-NAME>ISIS PHARMACEUTICALS INC
<CIK>0000874015
<ASSIGNED-SIC>2834
<IRS-NUMBER>330336973
<STATE-OF-INCORPORATION>DE
<FISCAL-YEAR-END>1231
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<BUSINESS-ADDRESS>
<STREET1>1896 RUTHERFORD ROAD
<CITY>CARLSBAD
<STATE>CA
<ZIP>92008
<PHONE>7609319200
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<STREET1>1896 RUTHERFORD ROAD
<CITY>CARLSBAD
<STATE>CA
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<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>

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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><font style="font-weight:bold;">August&nbsp;2, 2005</font></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 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>

<table border="0" cellspacing="0" cellpadding="0" width="100%" style="border-collapse:collapse;width:100.0%;">
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  <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 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>
 </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;"><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><font style="font-weight:bold;">(760) 931-9200</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 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">&nbsp;</font></p>

<table border="0" cellspacing="0" cellpadding="0" width="100%" style="border-collapse:collapse;width:100.0%;">
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  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font></p>
  </td>
  <td width="96%" valign="top" style="padding:0in 0in 0in 0in;width:96.0%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Written communications pursuant to Rule&nbsp;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" style="font-size:10.0pt;">&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 align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font></p>
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  <td width="599" valign="top" style="padding:0in 0in 0in 0in;width:449.3pt;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Soliciting material pursuant to Rule&nbsp;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" style="font-size:10.0pt;">&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 align="left" style="margin:0in 0in .0001pt;text-align:left;"><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 align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" 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>
  </td>
 </tr>
</table>

<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 align="left" style="margin:0in 0in .0001pt;text-align:left;"><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 align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" 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>
  </td>
 </tr>
</table>

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

</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="font-size:10.0pt;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</font></b><b><font size="1" style="font-size:3.0pt;font-weight:bold;">&#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>Entry
into a Material Agreement.</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:0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">On August&nbsp;2,
2005, Isis Pharmaceuticals,&nbsp;Inc. issued a press release announcing that
its Ibis division has been awarded a government grant for up to $4.9 million for
its TIGER biosensor system for the continued development of applications to
diagnose infectious disease and to identify and control hospital-associated
infections.&#160; The grant was received from
the National Institute of Allergy and Infectious Diseases (NIAID), part of the
National Institutes of Health (NIH).&#160; A
copy of this release is furnished with this report as an exhibit.</font></p>

<p 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;">&nbsp;</font></p>

<p align="left" style="font-size:10.0pt;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.</font></b><b><font size="1" style="font-size:3.0pt;font-weight:bold;">&#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>Financial
Statements and Exhibits.</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)&nbsp; 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="93%" style="border-collapse:collapse;margin-left:.5in;width:93.0%;">
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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;">99.1</font></p>
  </td>
  <td width="604" valign="top" style="padding:0in 0in 0in 0in;width:453.2pt;">
  <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 August&nbsp;2, 2005.</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;"><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>

<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:auto;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:auto;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-variant:normal !important;font-weight:normal;">&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;"><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;">&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:53.7%;">
  <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="2" valign="top" style="padding:0in 0in 0in 0in;width:46.3%;">
  <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="53%" valign="top" style="padding:0in 0in 0in 0in;width:53.7%;">
  <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="2" valign="top" style="padding:0in 0in 0in 0in;width:46.3%;">
  <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="53%" valign="top" style="padding:0in 0in 0in 0in;width:53.7%;">
  <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="2" valign="top" style="padding:0in 0in 0in 0in;width:46.3%;">
  <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="53%" valign="top" style="padding:0in 0in 0in 0in;width:53.7%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Dated:&nbsp;&nbsp;August&nbsp;2, 2005</font></p>
  </td>
  <td width="3%" valign="top" style="padding:0in 0in 0in 0in;width:3.7%;">
  <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:42.6%;">
  <p align="left" style="margin:0in 0in .0001pt;text-align:left;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;/s/ B. Lynne Parshall</font></p>
  </td>
 </tr>
 <tr>
  <td width="53%" valign="top" style="padding:0in 0in 0in 0in;width:53.7%;">
  <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:3.7%;">
  <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%" valign="top" style="border:none;padding:0in 0in 0in 0in;width:42.6%;">
  <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="53%" valign="top" style="padding:0in 0in 0in 0in;width:53.7%;">
  <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:3.7%;">
  <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%" valign="top" style="padding:0in 0in 0in 0in;width:42.6%;">
  <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>
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  <td width="53%" valign="top" style="padding:0in 0in 0in 0in;width:53.7%;">
  <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:3.7%;">
  <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%" valign="top" style="padding:0in 0in 0in 0in;width:42.6%;">
  <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>
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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;">3</font></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;">&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="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="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;&#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 August&nbsp;2, 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&nbsp;99.1</font></b></p>

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  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Navjot Rai</font></p>
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  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Investor Relations&nbsp;&amp; Corporate Communications </font></p>
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  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
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  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>
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  <p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">760-603-2331</font></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;">&nbsp;</font></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;text-autospace:none;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">ISIS PHARMACEUTICALS AWARDED GRANT FOR UP TO $4.9 MILLION FROM THE<br>
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES TO DEVELOP<br>
HEALTHCARE APPLICATIONS FOR TIGER BIOSENSOR SYSTEM</font></b></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;text-autospace:none;"><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-autospace:none;"><b><i><font size="2" face="Times New Roman" style="font-size:10.0pt;font-style:italic;font-weight:bold;">Collaboration with Leading Medical Centers Furthers
Development of</font></i></b></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;text-autospace:none;"><b><i><font size="2" face="Times New Roman" style="font-size:10.0pt;font-style:italic;font-weight:bold;">&#160;TIGER
Biosensor System for Clinical Diagnostics</font></i></b></p>

<p align="center" style="margin:0in 0in .0001pt;text-align:center;text-autospace:none;"><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;text-autospace:none;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">CARLSBAD, Calif., August&nbsp;2,
2005 </font></b>- Isis
Pharmaceuticals,&nbsp;Inc. (Nasdaq: ISIS) announced today that its Ibis
division has been awarded a government grant for up to $4.9 million for its
TIGER biosensor system for the continued development of applications to
diagnose infectious diseases and to identify and control hospital-associated
infections.&#160; The grant was received from
the National Institute of Allergy and Infectious Diseases (NIAID), part of the
National Institutes of Health (NIH).&#160; The
TIGER (Triangulation Identification for Genetic Evaluation of Risks) biosensor
system is a revolutionary system for the identification of infectious organisms
as it can simultaneously identify thousands of infectious organisms without needing
to know what might be present in a sample.</p>

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

<p style="margin:0in 0in .0001pt;text-autospace:none;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">As part of this three-year,
milestone-driven grant, Ibis will work closely with several of its long-term
clinical collaborators including the Johns Hopkins University Medical Center, ARUP
Laboratories, and Lovelace Respiratory Research Institute to test and validate
the TIGER biosensor system for clinical laboratory use.&#160; Ibis will also develop infectious organism
identification (ID) test kits to identify a broad range of respiratory and
blood-borne infectious agents.&#160; In
addition, Ibis will deliver a TIGER biosensor system to one of the medical
collaborators for clinical diagnostics validation.</font></p>

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

<p style="margin:0in 0in .0001pt;text-autospace:none;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&#147;This grant reflects the
very high level of excitement in the government about the potential of the
TIGER biosensor system to revolutionize the identification of infectious
diseases in a clinical setting, and represents a significant step forward in
commercializing its diagnostic and hospital-associated infection control
applications,&#148; said Michael Treble, President of Ibis and Vice President of
Isis. &#147;The collaborative work that we conduct with leading medical institutions
will provide data, documentation and experience to support the regulatory and
manufacturing approvals required to access the clinical diagnostics markets.&#148;</font></p>

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

<p style="margin:0in 0in .0001pt;text-autospace:none;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Ibis plans to deliver a
TIGER biosensor system this year to the U.S. Army Medical Research Institute of
Infectious Diseases (USAMRIID), for use in biological warfare defense; to the
Naval Health Research Center and to the Centers for Disease Control and
Prevention (CDC), each for use in epidemiological surveillance, and to the
Department of Homeland Security, for use in microbial forensics.</font></p>

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

<p style="margin:0in 0in .0001pt;text-autospace:none;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">From inception through March&nbsp;31,
2005, Ibis has earned $38.5 million in revenue from government partners. An
additional $15.2 million is committed under existing contracts and grants, with
the potential for added funding.</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-autospace:none;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">-more-</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>

<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" 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
TIGER AND THE IBIS DIVISION</font></b></p>

<p style="font-size:10.0pt;margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">The Ibis
division has </font>developed the TIGER (Triangulation Identification for
Genetic Evaluation of Risks) biosensor system, a revolutionary system to
identify infectious organisms.&#160; Ibis
plans to commercialize the TIGER biosensor system to government customers for
use in biowarfare defense,
epidemiological surveillance and forensics; and to non-government customers for
use in pharmaceutical process control, hospital-associated infection control
and infectious disease diagnostics.&#160; Additional information about Isis&#146; Ibis
division can be found at www.ibistiger.com or accessed from Isis&#146; homepage&nbsp;at
www.isispharm.com.</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;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">The Ibis
division has been funded by U.S. government agencies including the Defense
Advanced Research Projects Agency (DARPA), the National Institute of Allergy
and Infectious Diseases (NIAID), part of the National Institutes of Health
(NIH), the Centers for Disease Control and Prevention (CDC), the Federal Bureau
of Investigation (FBI), the Department of Homeland Security (DHS) and others.</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;text-autospace:none;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">ABOUT ISIS
PHARMACEUTICALS, INC.</font></b></p>

<p style="margin:0in 0in .0001pt;text-autospace:none;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Isis Pharmaceuticals,&nbsp;Inc.
is exploiting its expertise in RNA to discover and develop novel drugs for its
product pipeline and for its partners.&#160;
The Company has successfully commercialized the world&#146;s first antisense
drug and has 11 antisense drugs
in development to treat metabolic, cardiovascular and inflammatory diseases,
and cancer. In its Ibis
division, Isis is developing and commercializing the TIGER biosensor system, a
revolutionary 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.&#160; Additional information
about Isis is available at www.isispharm.com.</font></p>

<p style="margin:0in 0in .0001pt;text-autospace:none;"><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 the development and
commercialization of Isis Pharmaceuticals&#146; TIGER biosensor system, as well as the
Company&#146;s plans and goals for Ibis.&#160; Any statement describing Isis&#146; 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; goals.&#160; Such
statements are subject to certain risks and uncertainties, particularly those
inherent in developing and commercializing systems to identify infectious
organisms that are effective and commercially attractive, and in the endeavor
of building a business around such products.&#160;
Isis&#146; forward-looking statements also involve assumptions that, if they
never materialize or prove correct, could cause its results to differ
materially from those expressed or implied by such forward-looking
statements.&#160; Although Isis&#146;
forward-looking statements reflect the good faith judgment of its management,
these statements are based only on facts and factors currently known by
Isis.&#160; As a result, you are cautioned not
to rely on these forward-looking statements.&#160;
These and other risks concerning Isis&#146; programs are described in
additional detail in Isis&#146; annual report on Form&nbsp;10-K for the year ended December&nbsp;31,
2004, and its quarterly report on Form&nbsp;10-Q for the quarter ended March&nbsp;31,
2005, which are on file with the SEC.&#160;
Copies of these and other documents are available from the Company.</font></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;"># # #</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>

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