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 7, 2005

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.)

2292 Faraday Avenue

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 1.01 Entry into a Material Agreement.

On April 7, 2005, Isis Pharmaceuticals, Inc. (the “Company”) amended its Rights Agreement with American Stock Transfer and Trust Company dated December 8, 2000 (the “Rights Agreement”) to include a three-year independent director evaluation provision (the “TIDE Provision”).

The TIDE Provision requires an independent committee of the Company’s Board of Directors to review the Rights Agreement every three years and evaluate whether the Rights Agreement still is in the Company’s and its stockholders’ best interests.

Item 9.01. Financial Statements and Exhibits.

99.1

Amendment No.1 to Rights Agreement dated April 7, 2005.

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 7, 2005	By:	/s/ B. Lynne Parshall
		B. LYNNE PARSHALL
		Executive Vice President,
		Chief Financial Officer and Director

INDEX TO EXHIBITS

99.1

Amendment No. 1 to Rights Agreement dated April 7, 2005.