Sec Form 4 Filing - PARSHALL B LYNNE @ ISIS PHARMACEUTICALS INC - 2014-01-29

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

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1. Name and Address of Reporting Person PARSHALL B LYNNE 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) COO (Last) (First) (Middle) C/O ISIS PHARMACEUTICALS, INC., 2855 GAZELLE COURT 3. Date of Earliest Transaction (MM/DD/YY) 01/29/2014 (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 01/29/2014 01/29/2014 M( 1 ) 3,972 ( 1 ) A $ 11.27 7,994 D Common Stock 01/29/2014 01/29/2014 S( 1 ) 3,972 ( 1 ) D $ 48.807 4,022 D Common Stock 01/29/2014 01/29/2014 M( 1 ) 31,028 ( 1 ) A $ 10.29 35,050 D Common Stock 01/29/2014 01/29/2014 S( 1 ) 31,028 ( 1 ) D $ 48.807 4,022 D Common Stock 01/29/2014 01/29/2014 M( 1 ) 5,000 ( 1 ) A $ 7.25 5,000 I By daughter Common Stock 01/29/2014 01/29/2014 S( 1 ) 5,000 ( 1 ) D $ 48.807 0 I By daughter Common Stock 01/29/2014 01/29/2014 M( 1 ) 5,000 ( 1 ) A $ 7.25 5,000 I By daughter Common Stock 01/29/2014 01/29/2014 S( 1 ) 5,000 ( 1 ) D $ 48.807 0 I By daughter Common Stock 01/29/2014 01/29/2014 M( 1 ) 5,000 ( 1 ) A $ 7.25 5,000 I By son-in-law Common Stock 01/29/2014 01/29/2014 S( 1 ) 5,000 ( 1 ) D $ 48.807 0 I By son-in-law Common Stock 01/30/2014 01/30/2014 M( 1 ) 23,635 ( 1 ) A $ 10.29 27,657 D Common Stock 01/30/2014 01/30/2014 S( 1 ) 23,635 ( 1 ) D $ 50.364 4,022 D Common Stock 01/30/2014 01/30/2014 M( 1 ) 15,875 ( 1 ) A $ 7.25 19,897 D Common Stock 01/30/2014 01/30/2014 S( 1 ) 15,875 ( 1 ) D $ 50.364 4,022 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) $ 11.27 01/29/2014 01/29/2014 M 3,972 01/04/2014 01/03/2017 Common Stock 3,972 $ 0 0 D Employee Stock Option (right to buy) $ 10.29 01/29/2014 01/29/2014 M 31,028 01/03/2015( 2 ) 01/02/2018 Common Stock 31,028 $ 0 41,856 D Employee Stock Option (right to buy) $ 7.25 01/29/2014 01/29/2014 M 5,000 01/03/2013 01/02/2019 Common Stock 5,000 $ 0 0 I By daughter Employee Stock Option (right to buy) $ 7.25 01/29/2014 01/29/2014 M 5,000 01/03/2013 01/02/2019 Common Stock 5,000 $ 0 0 I By daughter Employee Stock Option (right to buy) $ 7.25 01/29/2014 01/29/2014 M 5,000 01/03/2013 01/02/2019 Common Stock 5,000 $ 0 0 I By son-in-law Employee Stock Option (right to buy) $ 10.29 01/30/2014 01/30/2014 M 23,635 01/03/2015( 2 ) 01/02/2018 Common Stock 23,635 $ 0 18,221 D Employee Stock Option (right to buy) $ 7.25 01/30/2014 01/30/2014 M 15,875 01/02/2016( 3 ) 01/02/2019 Common Stock 15,875 $ 0 30,874 D

Reporting Owners Reporting Owner Name / Address Relationships Director 10% Owner Officer Other PARSHALL B LYNNE C/O ISIS PHARMACEUTICALS, INC. 2855 GAZELLE COURT CARLSBAD, CA92010 X COO Signatures /s/B. Lynne Parshall 01/30/2014 Signature of Reporting Person Date

Explanation of Responses:

( 1 )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 12/30/13. ( 2 )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 vested and became exercisable on 1/3/12. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 18,221 shares per year. The option shall be fully vested and exercisable on 1/3/15. The option was exercisable as to 54,663 shares on 1/29/14. ( 3 )Grant of 1/3/12 to reporting person of stock options under the Isis Pharmaceuticals, Inc. 1989 Stock Option Plan. 25% of the shares subject to the option vested and became exercisable on 1/3/13. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 15,437 shares per year. The option shall be fully vested and exercisable on 1/3/16. The option was exercisable as to 15,875 shares on 1/30/14.

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).

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