Sec Form 4 Filing - Castleman Breaux @ ISIS PHARMACEUTICALS INC - 2015-07-01

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 Castleman Breaux 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 _____ Officer (give title below) _____ Other (specify below) (Last) (First) (Middle) C/O ISIS PHARMACEUTICALS, INC., 2855 GAZELLE COURT 3. Date of Earliest Transaction (MM/DD/YY) 07/01/2015 (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 07/01/2015 07/01/2015 M( 1 ) 938 A $ 0 2,345 D Common Stock 07/01/2015 07/01/2015 M( 2 ) 469 A $ 0 2,814 D Common Stock 07/01/2015 07/01/2015 M( 3 ) 667 A $ 0 3,481 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 Restricted Stock Units ( 4 ) 07/01/2015 07/01/2015 M 938 ( 5 ) ( 5 ) Common Stock 938 $ 0 1,874 D Restricted Stock Units ( 4 ) 07/01/2015 07/01/2015 M 469 ( 6 ) ( 6 ) Common Stock 469 $ 0 937 D Restricted Stock Units ( 4 ) 07/01/2015 07/01/2015 M 667 ( 7 ) ( 7 ) Common Stock 667 $ 0 2,000 D Restricted Stock Units ( 4 ) 07/01/2015 07/01/2015 A 2,667 ( 8 ) ( 8 ) Common Stock 2,667 $ 0 2,667 D Director Stock Option (right to buy) $ 57.16 07/01/2015 07/01/2015 A 16,000 07/01/2016( 9 ) 06/30/2025 Common Stock 16,000 $ 0 16,000 D

Reporting Owners Reporting Owner Name / Address Relationships Director 10% Owner Officer Other Castleman Breaux C/O ISIS PHARMACEUTICALS, INC. 2855 GAZELLE COURT CARLSBAD, CA92010 X Signatures /s/B. Lynne Parshall, attorney-in-fact 07/02/2015 Signature of Reporting Person Date

Explanation of Responses:

( 1 )Acquired pursuant to vesting and release of shares pursuant to an RSU award granted on June 25, 2013. ( 2 )Acquired pursuant to vesting and release of shares pursuant to an RSU award granted on July 1, 2013. ( 3 )Acquired pursuant to vesting and release of shares pursuant to an RSU award granted on July 1, 2014. ( 4 )Each Restricted Stock Unit represents a contingent right to receive one share of Isis common stock, or its equivalent cash value. ( 5 )Restricted Stock Unit Award granted on June 25, 2013. Restricted Stock Units vest in equal annual installments, the first installment vested on July 1, 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 July 1, 2017. ( 6 )Restricted Stock Unit Award granted on July 1, 2013. Restricted Stock Units vest in equal annual installments, the first installment vested on July 1, 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 July 1, 2017. ( 7 )Restricted Stock Unit Award granted on July 1, 2014. Restricted Stock Units vest in equal annual installments, the first installment vested on July 1, 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 July 1, 2018. ( 8 )Grant of July 1, 2015 to reporting person of Restricted Stock Unit Award under the Isis Pharmacueticals, Inc. Amended and Restated 2002 Non-Employee Directors' Stock Option Plan. Restricted Stock Units vest in four equal annual installments, the first installment vesting on July 1, 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 July 1, 2019. The RSU is vested as to 0 shares on July 1, 2015. ( 9 )Grant of July 1, 2015 to reporting person of stock options under the Isis Pharmacueticals, Inc. Amended & Restated 2002 Non-Employee Directors' Stock Option Plan. The option vests and becomes exercisable in four equal annual installments, the first installment vesting on July 1, 2016. The option shall be fully vested and exercisable on July 1, 2019. The stock option was exercisable as to 0 shares on July 1, 2015.

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