UNITED STATES
                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549

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                                  SCHEDULE 13G

                    Under the Securities Exchange Act of 1934


                           ISIS PHARMACEUTICALS, INC.
                                (Name of Issuer)

                         Common Stock, $0.001 Par Value
                         (Title of Class of Securities)

                                   4643300109
                                 (CUSIP Number)

                            Wayne P. Merkelson, Esq.
                              Novartis Corporation
                                564 Morris Avenue
                              Summit, NJ 07901-1398
                            Telephone: (908) 522-6777
                     (Name, Address and Telephone Number of
                    Person Authorized to Receive Notices and
                                 Communications)

                                    Copy to:

                             Spencer D. Klein, Esq.
                               Shearman & Sterling
                              599 Lexington Avenue
                            New York, New York 10022
                            Telephone: (212) 848-4000

               Check the appropriate box to designate the rule pursuant to which
this Schedule is filed:

                                |_| Rule 13d-1(b)
                                |X| Rule 13d-1(c)
                                |_| Rule 13d-1(d)
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CUSIP No. 4643300109 (1) Name of Reporting Person S.S. or I.R.S. Identification No. of Above Person Novartis AG (2) Check the Appropriate Box if a Member of Group (See Instructions) |_| (a) |_| (b) (3) SEC Use Only (4) Citizenship or Place of Organization Switzerland Number of (5) Sole Voting Power 0 ---------------------------------- Shares ---------------------------------------------------- Beneficially (6) Shared Voting Power 2,354,150 --------------------------------- Owned by ---------------------------------------------------- Each (7) Sole Dispositive Power 0 --------------------------- Reporting ---------------------------------------------------- Person (8) Shared Dispositive Power 2,354,150 ---------------------------------------------------- With - ------- ------------------------------------------------------------- (9) Aggregate Amount Beneficially Owned by Each Reporting Person 2,354,150 ---------- (10) Check if the Aggregate Amount in Row (9) Excludes Certain Shares (See Instructions) (11) Percent of Class Represented by Amount in Row (9) 8.75% (12) Type of Reporting Person (See Instructions) CO

CUSIP No. 4643300109 (1) Name of Reporting Person S.S. or I.R.S. Identification No. of Above Person Novartis Pharma AG (2) Check the Appropriate Box if a Member of Group (See Instructions) |_| (a) |_| (b) (3) SEC Use Only (4) Citizenship or Place of Organization Switzerland Number of (5) Sole Voting Power 0 ---------------------------------- Shares ---------------------------------------------------- Beneficially (6) Shared Voting Power 2,219,000 --------------------------------- Owned by ---------------------------------------------------- Each (7) Sole Dispositive Power 0 ------------------------------ Reporting ---------------------------------------------------- Person (8) Shared Dispositive Power 2,219,000 ------------------------------------- With - ------- ------------------------------------------------------------- (9) Aggregate Amount Beneficially Owned by Each Reporting Person 2,219,000 ---------- (10) Check if the Aggregate Amount in Row (9) Excludes Certain Shares (See Instructions) (11) Percent of Class Represented by Amount in Row (9) 8.25% (12) Type of Reporting Person (See Instructions) CO

CUSIP No. 4643300109 (1) Name of Reporting Person S.S. or I.R.S. Identification No. of Above Person Novartis Pharmaceuticals Corporation (2) Check the Appropriate Box if a Member of Group (See Instructions) |_| (a) |_| (b) (3) SEC Use Only (4) Citizenship or Place of Organization Delaware Number of (5) Sole Voting Power 0 ---------------------------------- Shares ---------------------------------------------------- Beneficially (6) Shared Voting Power 38,053 --------------------------------- Owned by ---------------------------------------------------- Each (7) Sole Dispositive Power 0 ------------------------------ Reporting ---------------------------------------------------- Person (8) Shared Dispositive Power 38,053 ------------------------------------- With - ------- ------------------------------------------------------------- (9) Aggregate Amount Beneficially Owned by Each Reporting Person 38,053 ---------- (10) Check if the Aggregate Amount in Row (9) Excludes Certain Shares (See Instructions) (11) Percent of Class Represented by Amount in Row (9) 0.14% (12) Type of Reporting Person (See Instructions) CO

CUSIP No. 4643300109 (1) Name of Reporting Person S.S. or I.R.S. Identification No. of Above Person Genetic Therapy, Inc. (2) Check the Appropriate Box if a Member of Group (See Instructions) |_| (a) |_| (b) (3) SEC Use Only (4) Citizenship or Place of Organization Delaware Number of (5) Sole Voting Power 0 ---------------------------------- Shares ---------------------------------------------------- Beneficially (6) Shared Voting Power 97,097 --------------------------------- Owned by ---------------------------------------------------- Each (7) Sole Dispositive Power 0 ------------------------------ Reporting ---------------------------------------------------- Person (8) Shared Dispositive Power 97,097 ------------------------------------- With - ------- ------------------------------------------------------------- (9) Aggregate Amount Beneficially Owned by Each Reporting Person 97,097 ---------- (10) Check if the Aggregate Amount in Row (9) Excludes Certain Shares (See Instructions) (11) Percent of Class Represented by Amount in Row (9) 0.36% (12) Type of Reporting Person (See Instructions) CO

Item 1. Issuer (a) Isis Pharmaceuticals, Inc. (b) 2292 Faraday Avenue Carlsbad, California 92008 Item 2. Persons Filing (a) Name of Person Filing: Novartis AG ("Novartis"), Novartis Pharma AG, Novartis Pharmaceuticals Corporation and Genetic Therapy, Inc. (b) Address of Principal Offices: (i) The principal offices of Novartis are located at Schwarzwaldallee 215, CH-4002, Basel, Switzerland. (ii) The principal offices of Novartis Pharma AG are located at Lichtstrasse 35, CH-4002, Basel, Switzerland. (iii) The principal offices of Novartis Pharmaceuticals Corporation are located at 59 Route 10, East Hanover, New Jersey 07936. (iv) The principal offices of Genetic Therapy, Inc. are located at 938 Clopper Road, Gaithersburg, Maryland 20878. (c) Citizenship: Novartis and Novartis Pharma AG are Swiss corporations. Novartis Pharmaceuticals Corporation and Genetic Therapy, Inc. are Delaware corporations. (d) Title of Class of Securities: Common Stock, $0.001 par value. (e) CUSIP Number: 464300109 Item 3. This statement is filed pursuant to ss.240.13d-1(c). Item 4. Ownership (a) Novartis Pharma AG owns 2,219,000 shares of Common Stock, Novartis Pharmaceuticals Corporation owns 38,053 shares of Common Stock and Genetic Therapy, Inc. owns 97,097 shares of Common Stock. By virtue of the shares held by Novartis Pharma AG, Novartis Pharmaceuticals Corporation and Genetic Therapy, Inc., Novartis, as the ultimate parent entity, beneficially owns 2,354,150 shares of Common Stock. (b) Together the shares of Common Stock held by Novartis Pharma AG, Novartis Pharmaceuticals Corporation and Genetic Therapy, Inc. constitute approximately 8.75% of the outstanding Common Stock of the Issuer. Item 5. Ownership of Five Percent or Less of a Class Not applicable. Item 6. Ownership of More than Five Percent on Behalf of Another Person

Not applicable. Item 7. Identification and Classification of the Subsidiary Which Acquired the Security Being Reported on by the Parent Holding Company Not applicable. Item 8. Identification and Classification of Members of the Group Not Applicable. Item 9. Notice of Dissolution of Group Not Applicable. Item 10. Certification if Statement Filed Pursuant to Rule 13d-1(c) (a) Not applicable. (b) By signing below I certify that, to the best of my knowledge and belief, the securities referred to above were not acquired and are not held for the purpose of or with the effect of changing or influencing the control of the issuer of the securities and were not acquired and are not held in connection with or as a participant in any transaction having that purpose or effect.

SIGNATURE After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct. Date: February 13, 1999 NOVARTIS AG By: /s/ Dr. Urs Baerlocher Name: Dr. Urs Baerlocher Title: General Counsel By: /s/ Martin Henrich Name: Martin Henrich Title: Associate General Counsel

SIGNATURE After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct. Date: February 10, 1999 NOVARTIS PHARMA AG By: /s/ Joseph Mamie Name: Joseph Mamie Title: Pharma Finance, Financial Investment By: /s/ Olivier Bassi Name: Olivier Bassi Title: Senior Legal Counsel

SIGNATURE After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct. Date: February 11, 1999 NOVARTIS PHARMACEUTICALS CORPORATION By: /s/ Kenneth P. Schuster Name: Kenneth P. Schuster Title: Vice President and Controller By: /s/ Urs A. Naegelin Name: Urs A. Naegelin Title: Senior Vice President and CFO Finance and Administration

SIGNATURE After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct. Date: February 10, 1999 GENETIC THERAPY, INC. By: /s/ James T. DePalma Name: James T. DePalma Title: Vice President and Chief Financial Officer Finance and Information Technology