FORM 4

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

    Check this box if no longer subject to Section 16. Form 4 or Form 5 obligations may continue. See Instruction 1(b).

STATEMENT OF CHANGES IN BENEFICIAL OWNERSHIP

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

OMB Number: 3235-0287
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Filed By Romeo & Dye's Instant Form 4 Filer
www.section16.net

1. Name and Address of Reporting Person*

Crooke Stanley T.

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

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

Chairman, President and CEO                       

(Last)      (First)     (Middle)

2292 Faraday Avenue
 

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

(Street)

Carlsbad, CA 92008

(City)     (State)     (Zip)

Table I — Non-Derivative Securities Acquired, Disposed of, or Beneficially Owned

1. Title of Security
(Instr. 3)

2. Trans-
action
Date
(Month/ Day/
Year)

2A. Deemed
Execution
Date,
if any
(Month/Day/
Year)

3. Trans-
action Code
(Instr. 8)

4. Securities Acquired (A) or Disposed of (D)
(Instr. 3, 4 & 5)

5. Amount of
Securities
Beneficially
Owned Follow-
ing Reported Transactions(s)
(Instr. 3 & 4)

6. Owner-
ship Form:
Direct (D)
or Indirect (I)
(Instr. 4)

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

Code

V

Amount

(A)
or
(D)

Price

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

1. Title of Derivative Security

(Instr. 3)

2. Conver-
sion or
Exercise
Price of Derivative Security

3. Trans-
action Date

(Month/
Day/
Year)

4. Trans-
action
Code

(Instr. 8)

5. Number of Derivative Securities Acquired (A) or Disposed of (D)

(Instr. 3, 4 & 5)

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

7. Title and Amount of Underlying Securities
(Instr. 3 & 4)

8. Price of Derivative Security
(Instr. 5)

9. Number of
Derivative
Securities
Beneficially
Owned
Following
Reported Transaction(s)
(Instr. 4)

10. Owner-
ship Form
of Deriv-
ative
Security:
Direct (D)
or Indirect (I)
(Instr. 4)

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

Code

V

(A)

(D)

Date Exer-cisable

Expira-
tion
Date

Title

Amount or Number of
Shares

Employee Stock Option (right to buy)

$6.84

1-2-03

1-2-03

A

50,000

 ⁽¹⁾

1-1-13

Common Stock

50,000

50,000

D

Employee Stock Option (right to buy)

$6.84

1-2-03

1-2-03

A

2,567

 ⁽²⁾

1-1-13

Common Stock

2,567

2,567

I

By wife

Explanation of Responses:

(1) 25% of the shares subject to the option will vest and become exercisable on 1-2-04. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 12,500 shares per year. The option is exercisable as to 0 shares on 1-2-03.
(2) Due to her part-time status, only 18.77679% of the shares, 482 shares, subject to the option will vest and become exercisable on 1-2-04. Thereafter, 1,443 shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 481 shares per year. The option is exercisable as to 0 shares on 1-2-03.

**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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