FORM 3

UNITED STATES SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

INITIAL STATEMENT OF BENEFICIAL OWNERSHIP OF SECURITIES

Filed pursuant to Section 16(a) of the Securities Exchange Act of 1934, Section 17(a) of the Public Utility Holding Company Act of 1935 or Section 30(h) of the Investment Company Act of 1940

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Romeo and Dye's
Section 16 Filer
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1. Name and Address of Reporting Person*

Holmlund Jon T.

2. Date of Event
Requiring Statement
Month/Day/Year
04/02/03

4. Issuer Name and Ticker or Trading Symbol
Isis Pharmaceuticals, Inc. (ISIS)

(Last)      (First)     (Middle)

2292 Faraday Avenue
 

3. I.R.S. Identification
Number of Reporting
Person, if an entity
(voluntary)

5. Relationship of Reporting Person(s)
to Issuer (Check all applicable)
    Director                          10% Owner
X Officer                            Other
(give title below)              (specify below)

Vice President                                    

(Street)

Carlsbad, CA 92008

(City)     (State)     (Zip)

Table I — Non-Derivative Securities Beneficially Owned

1. Title of Security
(Instr. 4)

2. Amount of
Securities
Beneficially
Owned
(Instr. 4)

3. Ownership Form:
Direct (D)
or Indirect (I)
(Instr. 5)

4. Nature of Indirect
Beneficial Ownership
(Instr. 5)

Common Stock

5,593

D

Table II - Derivative Securities Beneficially Owned
(e.g., puts, calls, warrants, options, convertible securities)

1. Title of Derivative Security
(Instr. 4)

2. Date Exercisable
and Expiration Date
(Month/Day/ Year)

3. Title and Amount of Securities
Underlying Derivative Security
(Instr. 4)

4. Conversion or
Exercise Price of
Derivative Security

5. Ownership Form
of Derivative
Security:
Direct (D)
or Indirect (I)
(Instr. 5)

6. Nature of Indirect Beneficial Ownership
(Instr. 5)

Date
Exercisable

Expiration
Date

Title          

Amount or
Number of
Shares

Employee Stock Option (right to buy)

01/01/2002

12/31/2007

Common Stock

8,750

12.3125

D

Employee Stock Option (right to buy)

01/01/2003

12/31/2008

Common Stock

10,000

12.9375

D

Employee Stock Option (right to buy)

 ⁽¹⁾

01/05/2010

Common Stock

30,000

6.8100

D

Employee Stock Option (right to buy)

 ⁽²⁾

02/28/2010

Common Stock

5,000

16.0000

D

Employee Stock Option (right to buy)

 ⁽³⁾

01/01/2011

Common Stock

8,000

9.6250

D

Employee Stock Option (right to buy)

 ⁽⁴⁾

01/01/2012

Common Stock

6,000

21.0500

D

Employee Stock Option (right to buy)

 ⁽⁵⁾

06/15/2012

Common Stock

25,000

7.4100

D

Employee Stock Option (right to buy)

 ⁽⁶⁾

01/01/2013

Common Stock

9,000

6.8400

D

Employee Stock Option (right to buy)

 ⁽⁷⁾

03/15/2013

Common Stock

10,000

4.1600

D

Explanation of Responses:

(1) 25% of the shares subject to the option vested and became exercisable on 01/06/2001. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 7,500 shares per year. The option is exercisable as to 10,000 shares on 04/02/2003.
(2) 25% of the shares subject to the option vested and became exercisable on 03/01/2001. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 1,250 shares per year. The option is exercisable as to 3,854 shares on 04/02/2003.
(3) 25% of the shares subject to the option vested and became exercisable on 01/02/2002. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 2,000 shares per year . The option is exercisable as to 4,500 shares on 04/02/2003.
(4) 25% of the shares subject to the option vested and became exercisable on 01/02/2003. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 1,500 shares per year. The option is exercisable as to 1,875 shares on 04/02/2003.
(5) 25% of the shares subject to the option vested and became exercisable on 06/16/2003. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 6,250 shares per year. The option is exercisable as to 0 shares on 04/02/2003.
(6) 25% of the shares subject to the option vested and became exercisable on 01/02/2004. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 2,250 shares per year. The option is exercisable as to 0 shares on 04/02/2003.
(7) 25% of the shares subject to the option vested and became exercisable on 03/16/2004. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 2,500 shares per year. The option is exercisable as to 0 shares on 04/02/2003.

**Intentional misstatements or omissions of facts constitute Federal Criminal Violations.
See 18 U.S.C. 1001 and 15 U.S.C. 78ff(a).

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