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SEC FORM 4 SEC Form 4
FORM 4 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
or Section 30(h) of the Investment Company Act of 1940 		 
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OMB Number: 3235-0287
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Check this box if no longer subject to Section 16. Form 4 or Form 5 obligations may continue. See Instruction 1(b).
1. Name and Address of Reporting Person*
Castleman Breaux
(Last) (First) (Middle)
C/O ISIS PHARMACEUTICALS, INC.
2855 GAZELLE COURT
(Street)
CARLSBAD CA 92010
(City) (State) (Zip)
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)
3. Date of Earliest Transaction (Month/Day/Year)
07/01/2014
4. If Amendment, Date of Original Filed (Month/Day/Year)
 6. Individual or Joint/Group Filing (Check Applicable Line)
X Form filed by One Reporting Person
Form filed by More than One Reporting Person
Table I - Non-Derivative Securities Acquired, Disposed of, or Beneficially Owned
1. Title of Security (Instr. 3) 2. Transaction Date (Month/Day/Year) 2A. Deemed Execution Date, if any (Month/Day/Year) 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 07/01/2014 07/01/2014 M(1) 469 A $0 469 D
Common Stock 07/01/2014 07/01/2014 M(2) 938 A $0 1,407 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 (Month/Day/Year) 3A. Deemed Execution Date, if any (Month/Day/Year) 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 (Month/Day/Year) 7. Title and Amount of Securities Underlying Derivative Security (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: 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 (3) 07/01/2014 07/01/2014 M 469 (4) (4) Common Stock 469 $0 1,406 D
Restricted Stock Units (3) 07/01/2014 07/01/2014 M 938 (5) (5) Common Stock 938 $0 2,812 D
Restricted Stock Units (3) 07/01/2014 07/01/2014 A 2,667 (6) (6) Common Stock 2,667 $0 2,667 D
Director Stock Option (right to buy) $35.53 07/01/2014 07/01/2014 A 16,000 07/01/2015(7) 06/30/2024 Common Stock 16,000 $0 16,000 D
Explanation of Responses:
1. Acquired pursuant to vesting and release of shares pursuant to a Restricted Stock Unit award granted on July 1, 2013.
2. Acquired pursuant to vesting and release of shares pursuant to a Restricted Stock Unit award granted on June 25, 2013.
3. Each Restricted Stock Unit represents a contingent right to receive one share of Isis common stock, or its equivalent cash value.
4. Restricted Stock Unit Award granted on July 1, 2013. Restricted Stock Units vest in equal annual installments, the first installment vesting 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.
5. Restricted Stock Unit Award granted on June 25, 2013. Restricted Stock Units vest in equal annual installments, the first installment vesting 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. Grant of July 1, 2014 to reporting person of stock options under the Amended and Restated Isis Pharmaceuticals, Inc. 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, 2015. The option shall be fully vested and exercisable on July 1, 2018. The option is exercisable as to 0 shares on July 1, 2014.
7. Grant of July 1, 2014 to reporting person of stock options under the Amended and Restated Isis Pharmaceuticals, Inc. 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, 2015. The option shall be fully vested and exercisable on July 1, 2018. The option is exercisable as to 0 shares on July 1, 2014.
Remarks:
/s/B. Lynne Parshall, attorney-in-fact 07/02/2014
** Signature of Reporting Person Date
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.
POWER OF ATTORNEY



Know all by these presents, that the undersigned hereby constitutes and appoints each of Stanley T. Crooke and B. Lynne Parshall, signing individually, the undersigned's true and lawful attorneys-in fact and agents to:

(1) execute for and on behalf of the undersigned, an officer, director or holder of 10% or more of a registered class of securities of Isis Pharmaceuticals, Inc. (Isis), Forms 3, 4 and 5 in accordance with Section 16(a) of the Securities Exchange Act of 1934, as amended (the Exchange Act) and the rules thereunder;

(2) do and perform any and all acts for and on behalf of the undersigned that may be necessary or desirable to complete and execute such Form 3, 4 or 5, complete and execute any amendment or amendments thereto, and timely file such forms or amendments with the United States Securities and Exchange Commission and any stock exchange or similar authority; and

(3) take any other action of any nature whatsoever in connection with the foregoing which, in the opinion of such attorney-in-fact, may be of benefit, in the best interest of, or legally required by, the undersigned, it being understood that the documents executed by such attorney-in-fact on behalf of the undersigned pursuant to this Power of Attorney shall be in such form and shall contain such terms and conditions as such attorney-in-fact may approve in such attorney-in-fact's discretion.

The undersigned hereby grants to each such attorney-in-fact full power and authority to do and perform any and every act and thing whatsoever requisite, necessary, or proper to be done in the exercise of any of the rights and powers herein granted, as fully to all intents and purposes as the undersigned might or could do if personally present, with full power of substitution or revocation, hereby ratifying and confirming all that such attorney-in-fact, or such attorney-in-fact's substitute or substitutes, will lawfully do or cause to be done by virtue of this power of attorney and the rights and powers herein granted.  The undersigned acknowledges that the foregoing attorneys-in-fact, in serving in such capacity at the request of the undersigned, are not assuming, nor is Isis assuming, any of the undersigned's responsibilities to comply with Section 16 of the Exchange Act.

This Power of Attorney shall remain in full force and effect until the earliest to occur of (a) the undersigned is no longer required to file Forms 3, 4 and 5 with respect to the undersigned's holdings of and transactions in securities issued by Isis, (b) revocation by the undersigned in a signed writing delivered to the foregoing attorneys-in-fact or (c) as to any attorney-in-fact individually, until such attorney-in-fact will no longer be employed by Isis.



IN WITNESS WHEREOF, the undersigned has caused this Power of Attorney to be executed as of this 25th day of June, 2013.





/S/Breaux B Castleman