Statement of Changes in Beneficial Ownership (4)

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 OF SECURITIES	OMB APPROVAL OMB Number: 3235-0287 Estimated average burden hours per response... 0.5
	Filed pursuant to Section 16(a) of the Securities Exchange Act of 1934 or Section 30(h) of the Investment Company Act of 1940

1. Name and Address of Reporting Person * BERTHELSEN SPENCER R	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/YYYY) 7/1/2015
(Street) CARLSBAD, CA 92010 (City)        (State)        (Zip)	4. If Amendment, Date Original Filed (MM/DD/YYYY)	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. Trans. Date	2A. Deemed Execution Date, if any	3. Trans. 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	7/1/2015	7/1/2015	M (1)		469	A	$0	60864	D
Common Stock	7/1/2015	7/1/2015	M (2)		667	A	$0	61531	D
Common Stock	7/2/2015	7/2/2015	M (3)		312	A	$0	61843	D
Common Stock								70   (4)	I	By Daughter

Table II - Derivative Securities Beneficially Owned ( e.g. , puts, calls, warrants, options, convertible securities)
1. Title of Derivate Security (Instr. 3)	2. Conversion or Exercise Price of Derivative Security	3. Trans. Date	3A. Deemed Execution Date, if any	4. Trans. 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		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 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	(5)	7/1/2015	7/1/2015	M			469	(6)	(6)	Common Stock	469	$0	937	D
Restricted Stock Units	(5)	7/1/2015	7/1/2015	M			667	(7)	(7)	Common Stock	667	$0	2000	D
Restricted Stock Units	(5)	7/2/2015	7/2/2015	M			312	(8)	(8)	Common Stock	312	$0	312	D
Restricted Stock Units	(5)	7/1/2015	7/1/2015	A		2667		(9)	(9)	Common Stock	2667	$0	2667	D
Director Stock Option (right to buy)	$57.16	7/1/2015	7/1/2015	A		16000		7/1/2016   (10)	6/30/2025   (10)	Common Stock	16000	$0	16000	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 July 1, 2014.
( 3)	Acquired pursuant to vesting and release of shares pursuant to a Restricted Stock Unit award granted on July 2, 2012.
( 4)	The reporting person disclaims beneficial ownership of all securities held by his daughter, and this report should not be deemed an admission that the reporting person is the beneficial owner of such securities for purposes of Section 16 or for any other purpose.
( 5)	Each Restricted Stock Unit represents a contingent right to receive one share of Isis common stock, or its equivalent cash value.
( 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)	Restricted Stock Unit Award granted on July 2, 2012. Restricted Stock Units vest in equal annual installments, the first installment vested on July 2, 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 July 2, 2016.
( 9)	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.
( 10)	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 7/1/2016. The option shall be fully vested and exercisable on 7/1/2019. The stock option was exercisable as to 0 shares on 7/1/2015.

Reporting Owners
Reporting Owner Name / Address	Relationships
	Director	10% Owner	Officer	Other
BERTHELSEN SPENCER R C/O ISIS PHARMACEUTICALS, INC. 2855 GAZELLE COURT CARLSBAD, CA 92010	X

Signatures
/s/B. Lynne Parshall, attorney-in-fact		7/2/2015
** 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 control number.