October 28, 2005
VIA FACSIMILE & EDGAR
Securities and Exchange Commission
Division of Corporation Finance
450 Fifth Street, NW
Washington, DC 20549
RE: | Isis Pharmaceuticals, Inc. |
| Form S-3 Registration Statement No. 333-128156 |
Ladies and Gentlemen:
Pursuant to Rule 461 of Regulation C of the Securities Act of 1933, as amended, the undersigned registrant hereby requests that the Commission take appropriate action to cause the above-referenced Registration Statement No. 333-128156 to become effective at 5:00 p.m. Eastern Time on November 1, 2005 or as soon thereafter as is practicable.
Very truly yours,
ISIS PHARMACEUTICALS, INC.
By: | /s/ Patrick O’Neil |
|
| Patrick O’Neil, Esq. |
|
| Associate General Counsel |
|
B. Lynne Parshall, Esq. | |
| Grantland E. Bryce, Esq. |
