Sec Form 4 Filing - PARSHALL B LYNNE @ IONIS PHARMACEUTICALS INC - 2016-09-01

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 PARSHALL B LYNNE 2. Issuer Name and Ticker or Trading Symbol IONIS PHARMACEUTICALS INC [ IONS] 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 IONIS PHARMACEUTICALS, INC., 2855 GAZELLE COURT 3. Date of Earliest Transaction (MM/DD/YY) 09/01/2016 (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 09/01/2016 09/01/2016 M( 1 ) 8,865 ( 1 ) A $ 7.25 25,558 D Common Stock 09/01/2016 09/01/2016 S( 1 ) 8,865 ( 1 ) D $ 29.8154 ( 2 ) 16,693 D Common Stock 09/01/2016 09/01/2016 M( 1 ) 3,635 ( 1 ) A $ 14.69 20,328 D Common Stock 09/01/2016 09/01/2016 S( 1 ) 3,635 ( 1 ) D $ 30.05 16,693 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 Options (right to buy) $ 7.25 09/01/2016 09/01/2016 M 8,865 01/03/2016 01/02/2019 Common Stock 8,865 $ 0 0 D Employee Stock Option (right to buy) $ 14.69 09/01/2016 09/01/2016 M 3,635 01/02/2014( 3 ) 01/29/2020 Common Stock 3,635 $ 0 24,910 D

Reporting Owners Reporting Owner Name / Address Relationships Director 10% Owner Officer Other PARSHALL B LYNNE C/O IONIS PHARMACEUTICALS, INC. 2855 GAZELLE COURT CARLSBAD, CA92010 X COO Signatures /s/B. Lynne Parshall 09/06/2016 Signature of Reporting Person Date

Explanation of Responses:

( 1 )Acquired as a result of exercising a stock option pursuant to Rule 10b5-1 Trading Plan. The purchase and sale reported on this Form 4 was effective pursuant to Rule 10b5-1 Trading Plan adopted by the reporting person on 7/13/2016. ( 2 )The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $29.80 to $30.05, inclusive. The reporting person undertakes to provide to Ionis Pharmaceuticals, Inc., any security holder of Ionis Pharmaceuticals, Inc. or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares sold at each separate price within the ranges set forth in footnote (2) on this Form 4. ( 3 )Grant of 1/30/2013 to reporting person of stock options under the Ionis Pharmaceuticals, Inc. 1989 Stock Option Plan. 25% of the shares subject to the option vested and became exercisable on 1/2/2014. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 15,570 shares per year. Following this transaction, the option was exercisable as to 18,422 on 9/1/2016.

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