Sec Form 4 Filing - CROOKE STANLEY T @ ISIS PHARMACEUTICALS INC - 2015-01-15

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

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1. Name and Address of Reporting Person CROOKE STANLEY T 2. Issuer Name and Ticker or Trading Symbol ISIS PHARMACEUTICALS INC [ ISIS] 5. Relationship of Reporting Person(s) to Issuer (Check all applicable) X __ Director _____ 10% Owner X __ Officer (give title below) _____ Other (specify below) Chairman and CEO (Last) (First) (Middle) C/O ISIS PHARMACEUTICALS, INC., 2855 GAZELLE COURT 3. Date of Earliest Transaction (MM/DD/YY) 01/15/2015 (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 01/15/2015 01/15/2015 M( 1 ) 2,977 ( 1 ) A $ 0 9,918 D Common Stock 01/16/2015 01/16/2015 S( 2 ) 1,574 ( 2 ) D $ 67.964 8,344 D Common Stock 01/15/2015 01/15/2015 M( 3 ) 5,548 ( 3 ) A $ 0 13,892 D Common Stock 01/16/2015 01/16/2015 S( 4 ) 2,933 ( 4 ) D $ 67.964 10,959 D Common Stock 01/15/2015 01/15/2015 M( 5 ) 7,813 ( 5 ) A $ 0 18,772 D Common Stock 01/16/2015 01/16/2015 S( 6 ) 4,130 ( 6 ) D $ 67.9645 14,642 D Common Stock 01/15/2015 01/15/2015 M( 1 ) 316 ( 1 ) A $ 0 943 I By wife Common Stock 01/16/2015 01/16/2015 S( 2 ) 121 ( 2 ) D $ 67.964 822 I By wife Common Stock 01/15/2015 01/15/2015 M( 7 ) 417 ( 7 ) A $ 0 1,239 I By wife Common Stock 01/16/2015 01/16/2015 S( 8 ) 160 ( 8 ) D $ 67.964 1,079 I By wife Common Stock 01/15/2015 01/15/2015 M( 5 ) 354 ( 5 ) A $ 0 1,433 I By wife Common Stock 01/16/2015 01/16/2015 S( 6 ) 136 ( 6 ) D $ 67.964 1,297 I By wife Common Stock 725,391 I By trust

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 Restricted Stock Units ( 9 ) 01/15/2015 01/15/2015 A 27,500 ( 10 ) ( 10 ) Common Stock 27,500 $ 0 27,500 D Restricted Stock Units ( 9 ) 01/15/2015 01/15/2015 A 1,450 ( 11 ) ( 11 ) Common Stock 1,450 $ 0 1,450 I By wife Restricted Stock Units ( 9 ) 01/15/2015 01/15/2015 M 2,977 ( 2 ) ( 12 ) ( 12 ) Common Stock 2,977 $ 0 2,977 D Restricted Stock Units ( 9 ) 01/15/2015 01/15/2015 M 5,548 ( 4 ) ( 13 ) ( 13 ) Common Stock 5,548 $ 0 11,094 D Restricted Stock Units ( 9 ) 01/15/2015 01/15/2015 M 7,813 ( 6 ) ( 14 ) ( 14 ) Common Stock 7,813 $ 0 23,437 D Restricted Stock Units ( 9 ) 01/15/2015 01/15/2015 M 316 ( 2 ) ( 12 ) ( 12 ) Common Stock 316 $ 0 316 I By wife Restricted Stock Units ( 9 ) 01/15/2015 01/15/2015 M 417 ( 8 ) ( 15 ) ( 15 ) Common Stock 417 $ 0 832 I By wife Restricted Stock Units ( 9 ) 01/15/2015 01/15/2015 M 354 ( 6 ) ( 14 ) ( 14 ) Common Stock 354 $ 0 1,062 I By wife

Reporting Owners Reporting Owner Name / Address Relationships Director 10% Owner Officer Other CROOKE STANLEY T C/O ISIS PHARMACEUTICALS, INC. 2855 GAZELLE COURT CARLSBAD, CA92010 X Chairman and CEO Signatures /s/B. Lynne Parshall, attorney-in-fact 01/20/2015 Signature of Reporting Person Date

Explanation of Responses:

( 1 )Acquired pursuant to vesting and release of shares pursuant to a RSU award granted on January 15, 2012. ( 2 )The sale was made pursuant to an automatic sale to cover the required tax withholding obligations pursuant to the 2011 Equity Incentive Plan Restricted Stock Unit Agreement and Grant Notice, dated January 15, 2012. ( 3 )Acquired pursuant to vesting and release of shares pursuant to a RSU award granted on January 30, 2013. ( 4 )The sale was made pursuant to an automatic sale to cover the required tax withholding obligations pursuant to the 2011 Equity Incentive Plan Restricted Stock Unit Agreement and Grant Notice, dated January 30, 2013. ( 5 )Acquired pursuant to vesting and release of shares pursuant to a RSU award granted on January 15, 2014. ( 6 )The sale was made pursuant to an automatic sale to cover the required tax withholding obligations pursuant to the 2011 Equity Incentive Plan Restricted Stock Unit Agreement and Grant Notice, dated January 15, 2014. ( 7 )Acquired pursuant to vesting and release of shares pursuant to a RSU award granted on January 15, 2013. ( 8 )The sale was made pursuant to an automatic sale to cover the required tax withholding obligations pursuant to the 2011 Equity Incentive Plan Restricted Stock Unit Agreement and Grant Notice, dated January 15, 2013. ( 9 )Each Restricted Stock Unit represents a contingent right to receive one share of Isis common stock, or its equivalent cash value. ( 10 )Grant 1/15/2015 to reporting person of Restricted Stock Units under the Isis Pharmaceuticals, Inc. 2011 Equity Incentive Plan. Restricted Stock Units vest in four equal annual installments, the first installment vesting on January 15, 2016. Upon vesting, the restricted stock units will be paid out in whole shares of Isis common stock or cash as may be determined by the Company. The RSU shall be fully vested on January 15, 2019. The RSU is vested as to 0 shares on January 15, 2015. ( 11 )Grant 1/15/2015 to reporting person's wife of Restricted Stock Units under the Isis Pharmaceuticals, Inc. 2011 Equity Incentive Plan. Restricted Stock Units vest in four equal annual installments, the first installment vesting on January 15, 2016. Upon vesting, the restricted stock units will be paid out in whole shares of Isis common stock or cash as may be determined by the Company. The RSU shall be fully vested on January 15, 2019. The RSU is vested as to 0 shares on January 15, 2015. ( 12 )Restricted Stock Unit Award granted on January 15, 2012. Restricted Stock Units vest in equal annual installments, the first installment vested on January 15, 2013. Upon vesting, the restricted stock units will be paid out in whole shares of Isis common stock or cash as may be determined by the Company. The RSU shall be fully vested on January 15, 2016. ( 13 )Restricted Stock Unit Award granted on January 30, 2013. Restricted Stock Units vest in equal annual installments, the first installment vested on January 15, 2014. Upon vesting, the restricted stock units will be paid out in whole shares of Isis common stock or cash as may be determined by the Company. The RSU shall be fully vested on January 15, 2017. ( 14 )Restricted Stock Unit Award granted on January 15, 2014. Restricted Stock Units vest in equal annual installments, the first installment vested on January 15, 2015. Upon vesting, the restricted stock units will be paid out in whole shares of Isis common stock or cash as may be determined by the Company. The RSU shall be fully vested on January 15, 2018. ( 15 )Restricted Stock Unit Award granted on January 15, 2013. Restricted Stock Units vest in equal annual installments, the first installment vested on January 15, 2014. Upon vesting, the restricted stock units will be paid out in whole shares of Isis common stock or cash as may be determined by the Company. The RSU shall be fully vested on January 15, 2017.

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