Sec Form 4 Filing - O'NEIL PATRICK R. @ ISIS PHARMACEUTICALS INC - 2013-01-29

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

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 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 APPROVAL OMB Number: 3235-0287 Expires: November 30, 2011 Estimated average burden hours per response... 0.5

1. Name and Address of Reporting Person O'NEIL PATRICK R. 2. Issuer Name and Ticker or Trading Symbol ISIS PHARMACEUTICALS INC [ ISIS] 5. Relationship of Reporting Person(s) to Issuer (Check all applicable) _____ Director _____ 10% Owner X __ Officer (give title below) _____ Other (specify below) SVP, Legal and General Counsel (Last) (First) (Middle) C/O ISIS PHARMACEUTICALS, INC., 2855 GAZELLE COURT 3. Date of Earliest Transaction (MM/DD/YY) 01/29/2013 (Street) CARLSBAD, CA92010 4. If Amendment, Date Original Filed (MM/DD/YY) 6. Individual or Joint/Group Filing (Check Applicable Line) __ X __ Form filed by One Reporting Person _____ Form filed by More than One Reporting Person (City) (State) (Zip)

Table I - Non-Derivative Securities Acquired, Disposed of, or Beneficially Owned 1.Title of Security (Instr. 3) 2. Transaction Date (MM/DD/YY) 2A. Deemed Execution Date, if any (MM/DD/YY) 3. Transaction Code (Instr. 8) 4. Securities Acquired (A) or Disposed of (D) (Instr. 3, 4 and 5) 5. Amount of Securities Beneficially Owned Following Reported Transaction(s) (Instr. 3 and 4) 6. Ownership Form: Direct (D) or Indirect (I) (Instr. 4) 7. Nature of Indirect Beneficial Ownership (Instr. 4) Code V Amount (A) or (D) Price Common Stock 01/29/2013 01/29/2013 S( 1 ) 300 ( 1 ) D $ 13.4 1,463 D Common Stock 01/30/2013 01/30/2013 M( 2 ) 2,000 ( 2 ) A $ 10.29 3,463 D Common Stock 01/30/2013 01/30/2013 S( 2 ) 2,000 ( 2 ) D $ 14.82 1,463 D

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. Conversion or Exercise Price of Derivative Security 3. Transaction Date (MM/DD/YY) 3A. Deemed Execution Date, if any (MM/DD/YY) 4. Transaction Code (Instr. 8) 5. Number of Derivative Securities Acquired (A) or Disposed of (D) (Instr. 3, 4, and 5) 6. Date Exercisable and Expiration Date (MM/DD/YY) 7. Title and Amount of Underlying Securities (Instr. 3 and 4) 8. Price of Derivative Security (Instr. 5) 9. Number of Derivative Securities Beneficially Owned Following Reported Transaction(s) (Instr. 4) 10. Ownership Form of Derivative Security: Direct (D) or Indirect (I) (Instr. 4) 11. Nature of Indirect Beneficial Ownership (Instr. 4) Code V (A) (D) Date Exercisable Expiration Date Title Amount or Number of Shares Employee Stock Option (right to buy) $ 10.29 01/30/2013 01/30/2013 M 2,000 01/03/2012( 3 ) 01/02/2018 Common Stock 2,000 $ 0 17,000 D

Reporting Owners Reporting Owner Name / Address Relationships Director 10% Owner Officer Other O'NEIL PATRICK R. C/O ISIS PHARMACEUTICALS, INC. 2855 GAZELLE COURT CARLSBAD, CA92010 SVP, Legal and General Counsel Signatures /s/Patrick R. O'Neil 01/30/2013 Signature of Reporting Person Date

Explanation of Responses:

( 1 )The sale reported in this Form 4 was effected pursuant to a Rule 10b5-1 trading plan adopted by the reporting person on 3/16/2012. ( 2 )Acquired as a result of exercising a stock option pursuant to a Rule 10b5-1 Trading Plan. The purchase and sale reported on this Form 4 was effective pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on 3/16/2012. ( 3 )Grant of 1/3/11 to reporting person of stock options under the Isis Pharmaceuticals, Inc. 1989 Stock Option Plan. 25% of the shares subject to the option vest and became exercisable on 1/3/12. Thereafter, the remaining shares subject to the option vest and become exerciable in 36 equal monthly installments, at the rate of 5,750 shares per year. The option was exercisable as to 7,500 shares on 1/30/13.

Reminder: Report on a separate line for each class of securities beneficially owned directly or indirectly.

* If the form is filed by more than one reporting person, see Instruction 4(b)(v).

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

Note: File three copies of this Form, one of which must be manually signed. If space is insufficient, see Instruction 6 for procedure.
Persons who respond to the collection of information contained in this form are not required to respond unless the form displays a currently valid OMB Number.