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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE 13G

Under the Securities Exchange Act of 1934
(Amendment No. 2)*

Isis Pharmaceuticals, Inc.
(Name of Issuer)
Common Stock
(Title of Class of Securities)
464330-1-09
(CUSIP Number)
May 23, 2005
(Date of Event Which Requires Filing of this Statement)

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

     o Rule 13d-1(b)

     þ Rule 13d-1(c)

     o Rule 13d-1(d)

* The remainder of this cover page shall be filled out for a reporting person’s initial filing on this form with respect to the subject class of securities, and for any subsequent amendment containing information which would alter the disclosures provided in a prior cover page.

The information required in the remainder of this cover page shall not be deemed to be “filed” for the purpose of Section 18 of the Securities Exchange Act of 1934 (“Act”) or otherwise subject to the liabilities of that section of the Act but shall be subject to all other provisions of the Act (however, see the Notes).

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.

 
 

 

                     
CUSIP No.
  
464330-1-09 
   Page  
2 
   of   
5 

 

           
1   NAMES OF REPORTING PERSONS:
Eli Lilly and Company
   
  I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY): 
    35-0470950
     
2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (SEE INSTRUCTIONS):
  (a)   o
  (b)   o      Not Applicable
     
3   SEC USE ONLY:
   
   
     
4   CITIZENSHIP OR PLACE OF ORGANIZATION:
   
  Indiana
       
  5   SOLE VOTING POWER:
     
NUMBER OF   2,500,000
       
SHARES 6   SHARED VOTING POWER:
BENEFICIALLY    
OWNED BY   None
       
EACH 7   SOLE DISPOSITIVE POWER:
REPORTING    
PERSON   2,500,000
       
WITH: 8   SHARED DISPOSITIVE POWER:
     
    None
     
9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON:
   
  2,500,000
     
10   CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES (SEE INSTRUCTIONS):
   
  o      Not Applicable
     
11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9):
   
  3.5%
     
12   TYPE OF REPORTING PERSON (SEE INSTRUCTIONS):
   
  CO

2

 

     
Item 1(a).
  Name of Issuer:
 
    
 
  Isis Pharmaceuticals, Inc.
 
    
Item 1(b).
  Address of Issuer’s Principal
 
  Executive Offices:
 
    
 
  2292 Faraday Avenue
 
  Carlsbad, CA 92008
 
    
Item 2(a).
  Name of Person Filing:
 
    
 
  Eli Lilly and Company
 
    
Item 2(b).
  Address of Principal Business
 
  Office or, if None, Residence:
 
    
 
  Lilly Corporate Center
 
  Indianapolis, IN 46285
 
    
Item 2(c).
  Citizenship:
 
    
 
  Indiana
 
    
Item 2(d).
  Title of Class of Securities:
 
    
 
  Common Stock
 
    
Item 2(e).
  CUSIP Number:
 
    
 
  464330-1-09
 
    
Item 3.
  If this statement is filed pursuant to Rule 13d-1(b), or 13d-2(b) or (c), check whether the person filing is a:
 
    
 
  (a)-(j)           Not applicable
 
    
 
  If this statement is filed pursuant to Rule 13d-1(c), check this box. [ X ]

Page 3 of 5 Pages

 

     
Item 4.
  Ownership.
     
(a)

   Amount Beneficially Owned:

  2,500,000
(b)

   Percent of Class:

  3.5%
(c)

   Number of shares as to which the person has:

  Sole voting power                         2,500,000

  Shared voting power                     None

  Sole dispositive power                  2,500,000
 
  Shared dispositive power              None
     
Item 5.
  Ownership of Five Percent or Less of a Class.     [X]
 
    
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

Page 4 of 5 Pages

 

     
Item 10.
  Certifications.
 
    
 
  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 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.
      
         
  ELI LILLY AND COMPANY
 		  
  By:   /s/ Charles E. Golden    
    Charles E. Golden   
    Executive Vice President and Chief Financial Officer   
 
Date: February 6, 2006

Page 5 of 5 Pages