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SECURITIES AND EXCHANGE COMMISSION
Washington, DC 20549

SCHEDULE 13G
(Rule 13d-102)

INFORMATION TO BE INCLUDED IN STATEMENTS FILED PURSUANT
TO RULES 13d-1(b) (c) AND (d) AND AMENDMENTS THERETO FILED
PURSUANT TO 13d-2(b)
(Amendment No. 5)1

    Flamel Technologies, S.A.
(Name of Issuer)		    

 
 
 
 
 
    Ordinary Shares
(Title of Class of Securities)		    

 
 
 
 
 
    338488 10 9
(CUSIP Number)		    

 
 
 
 
 
    December 31, 2004
(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)
x Rule 13d-1(c)
o Rule 13d-1(d)

1 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 purposes 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).

      
CUSIP NO. 338488 10 9   13G   Page 2 of 10 Pages
      
1   NAME OF REPORTING PERSON:
 Biotechnology Value Fund, L.P.
I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY):		    
2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP*   (a)  x
        (b)  o
         
3   SEC USE ONLY    

 
 
 
 
 
4   CITIZENSHIP OR PLACE OF ORGANIZATION

 
 
Delaware
 
 
    5   SOLE VOTING POWER
NUMBER OF       0
SHARES  
BENEFICIALLY   6   SHARED VOTING POWER
OWNED       661,442
BY  
EACH   7   SOLE DISPOSITIVE POWER
REPORTING       0
PERSON  
WITH:   8   SHARED DISPOSITIVE POWER
        661,442
9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON    

 
 
661,442
 
 
10   CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES*   o

 
 
 
 
 
11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)    

 
 
3.08%
 
 
12   TYPE OF REPORTING PERSON*    

 
 
PN
 
 

*SEE INSTRUCTIONS BEFORE FILLING OUT!

      
CUSIP NO. 338488 10 9   13G   Page 3 of 10 Pages
      
1   NAME OF REPORTING PERSON:
 Biotechnology Value Fund II, L.P.
I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY):		    
2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP*   (a)  x
        (b)  o
         
3   SEC USE ONLY    

 
 
 
 
 
4   CITIZENSHIP OR PLACE OF ORGANIZATION    

 
 
Delaware
 
 
    7   SOLE VOTING POWER
NUMBER OF       0
SHARES  
BENEFICIALLY   6   SHARED VOTING POWER
OWNED       775,570
BY  
EACH   7   SOLE DISPOSITIVE POWER
REPORTING       0
PERSON  
WITH:   8   SHARED DISPOSITIVE POWER
        775,570
9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON    

 
 
775,570
 
 
10   CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES*   o

 
 
 
 
 
11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)    

 
 
3.62%
 
 
12   TYPE OF REPORTING PERSON*    

 
 
PN
 
 

*SEE INSTRUCTIONS BEFORE FILLING OUT!

      
CUSIP NO. 338488 10 9   13G   Page 4 of 10 Pages
      
1   NAME OF REPORTING PERSON:
BVF Investments, L.L.C.
I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY):		    
2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP*   (a)  x
        (b)  o
         
3   SEC USE ONLY    

 
 
 
 
 
4   CITIZENSHIP OR PLACE OF ORGANIZATION    

 
 
Delaware
 
 
    5   SOLE VOTING POWER
NUMBER OF       0
SHARES  
BENEFICIALLY   6   SHARED VOTING POWER
OWNED       661,800
BY  
EACH   7   SOLE DISPOSITIVE POWER
REPORTING       0
PERSON  
WITH:   8   SHARED DISPOSITIVE POWER
        661,800
9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON    

 
 
661,800
 
 
10   CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES*   o

 
 
 
 
 
11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)    

 
 
3.09%
 
 
12   TYPE OF REPORTING PERSON*    

 
 
OO
 
 

*SEE INSTRUCTIONS BEFORE FILLING OUT!

      
CUSIP NO. 338488 10 9   13G   Page 5 of 10 Pages
      
1   NAME OF REPORTING PERSON:
 Investment 10, LLC
I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY):		    
2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP*   (a)  x
        (b)  o
         
3   SEC USE ONLY    

 
 
 
 
 
4   CITIZENSHIP OR PLACE OF ORGANIZATION    

 
 
Illinois
 
 
    5   SOLE VOTING POWER
NUMBER OF       0
SHARES  
BENEFICIALLY   6   SHARED VOTING POWER
OWNED       111,620
BY  
EACH   7   SOLE DISPOSITIVE POWER
REPORTING       0
PERSON  
WITH:   8   SHARED DISPOSITIVE POWER
        111,620
9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON    

 
 
111,620
 
 
10   CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES*   o

 
 
 
 
 
11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)    

 
 
0.52%
 
 
12   TYPE OF REPORTING PERSON*    

 
 
OO
 
 

*SEE INSTRUCTIONS BEFORE FILLING OUT!

      
CUSIP NO. 338488 10 9   13G   Page 6 of 10 Pages
      
1   NAME OF REPORTING PERSON:
 BVF Partners L.P.
S.S. OR I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY):		    
2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP*   (a)  x
        (b)  o
         
3   SEC USE ONLY    

 
 
 
 
 
4   CITIZENSHIP OR PLACE OF ORGANIZATION    

 
 
Delaware
 
 
    5   SOLE VOTING POWER
NUMBER OF       0
SHARES  
BENEFICIALLY   6   SHARED VOTING POWER
OWNED       2,210,432
BY  
EACH   7   SOLE DISPOSITIVE POWER
REPORTING       0
PERSON  
WITH:   8   SHARED DISPOSITIVE POWER
        2,210,432
9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON    

 
 
2,210,432
 
 
10   CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES*   o

 
 
 
 
 
11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)    

 
 
10.31% (See Item 2(d))
 
 
12   TYPE OF REPORTING PERSON*    

 
 
PN
 
 

*SEE INSTRUCTIONS BEFORE FILLING OUT!

      
CUSIP NO. 338488 10 9   13G   Page 7 of 10 Pages
      
1   NAME OF REPORTING PERSON:
 BVF Inc.
S.S. OR I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY):		    
2   CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP*   (a)  x
        (b)  o
         
3   SEC USE ONLY    

 
 
 
 
 
4   CITIZENSHIP OR PLACE OF ORGANIZATION    

 
 
Delaware
 
 
    5   SOLE VOTING POWER
NUMBER OF       0
SHARES  
BENEFICIALLY   6   SHARED VOTING POWER
OWNED       2,210,432
BY  
EACH   7   SOLE DISPOSITIVE POWER
REPORTING       0
PERSON  
WITH:   8   SHARED DISPOSITIVE POWER
        2,210,432
9   AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON    

 
 
2,210,432
 
 
10   CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES*   o

 
 
 
 
 
11   PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)    

 
 
10.31% (See Item 2(d))
 
 
12   TYPE OF REPORTING PERSON*    

 
 
IA, CO
 
 

*SEE INSTRUCTIONS BEFORE FILLING OUT!

      
CUSIP NO. 338488 10 9   13G   Page 8 of 10 Pages
      

ITEM 1(a). NAME OF ISSUER:

    Flamel Technologies, S.A. ("Flamel")

ITEM 1(b). ADDRESS OF ISSUER'S PRINCIPAL EXECUTIVE OFFICES:

    Parc Club Du Moulin A Vent
33 Avenue Du Docteur Georges Levy
69693 Venissieux Cedex
France

ITEM 2(a). NAME OF PERSON FILING:

        This Amendment to Schedule 13G is being filed on behalf of the following persons (the "Reporting Persons"):

        (i)
        Biotechnology Value Fund, L.P. ("BVF")
        (ii)
        Biotechnology Value Fund II, L.P. ("BVF2")
        (iii)
        BVF Investments, L.L.C. ("Investments")
        (iv)
        Investment 10, L.L.C. ("ILL10")
        (v)
        BVF Partners L.P. ("Partners")
        (vi)
        BVF Inc. ("BVF Inc.")

ITEM 2(b). ADDRESS OF PRINCIPAL BUSINESS OFFICE:

        The principal business office of the Reporting Persons comprising the group filing this Amendment to Schedule 13G is located at 227 West Monroe Street, Suite 4800, Chicago, Illinois, 60606.

ITEM 2(c). CITIZENSHIP:

    BVF:   a Delaware limited partnership
    BVF2:   a Delaware limited partnership
    Investments:   a Delaware limited liability company
    ILL10:   an Illinois limited liability company
    Partners:   a Delaware limited partnership
    BVF Inc.:   a Delaware corporation

ITEM 2(d). TITLE OF CLASS OF SECURITIES:

         This Amendment to Schedule 13G is being filed with respect to the French Ordinary Shares represented by American Depositary Shares ("Ordinary Shares") of Flamel. The Reporting Persons' percentage ownership of Ordinary Shares is based on 21,446,590 shares being outstanding, as advised by Flamel, and the ownership of 400,000 warrants (the "Warrants") by the Reporting Persons to purchase an equivalent number of Ordinary Shares.

        On October 28, 2004, the Reporting Persons acquired greater than ten percent of the Ordinary Shares of Flamel.

        As of December 31, 2004, (i) BVF beneficially owned 661,442 Ordinary Shares, of which 120,000 shares are attributable to Warrants; (ii) BVF2 beneficially owned 775,570 Ordinary Shares, of which 260,000 shares are attributable to Warrants; (iii) Investments beneficially owned 661,800 Ordinary Shares, none of which are attributable to Warrants; and (iv) ILL10 beneficially owned 111,620 Ordinary Shares, of which 20,000 shares are attributable to Warrants.

ITEM 2(e). CUSIP Number:

        338488 10 9

     
CUSIP NO. 338488 10 9   13G   Page 9 of 10 Pages
      

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: One of the following

        Not applicable as this Amendment to Schedule 13G is filed pursuant to Rule 13d-1(c).

ITEM 4. OWNERSHIP:

        The information in items 1 and 5 through 11 on the cover pages (pp. 2 - 7) on this Amendment to Schedule 13G is hereby incorporated by reference.

ITEM 5. OWNERSHIP OF FIVE PERCENT OR LESS OF A CLASS:

        If this statement is being filed to report the fact that as of the date hereof the Reporting Persons have ceased to be the beneficial owner of more than five percent of the class of securities check the following. o

ITEM 6. OWNERSHIP OF MORE THAN FIVE PERCENT ON BEHALF OF ANOTHER PERSON:

        BVF shares voting and dispositive power over the Ordinary Shares it beneficially owns with Partners. BVF2 also shares voting and dispositive power over the Ordinary Shares it beneficially owns with Partners. Investments also shares voting and dispositive power over the Ordinary Shares it beneficially owns with Partners. Pursuant to the operating agreement of Investments, Partners is authorized, among other things, to invest the funds of Ziff Asset Management, L.P., the majority member of Investments, in Ordinary Shares Investments beneficially owns and to vote and exercise dispositive power over those Ordinary Shares. Partners and BVF Inc. share voting and dispositive power over the Ordinary Shares beneficially owned by BVF, BVF2, Investments and those owned by ILL10, on whose behalf Partners acts as investment manager and, accordingly, Partners and BVF Inc. have beneficial ownership of all of the Ordinary Shares owned by such parties.

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 A GROUP:

        Not applicable.

ITEM 9. NOTICE OF DISSOLUTION OF GROUP:

        Not applicable.

     
CUSIP NO. 338488 10 9   13G   Page 10 of 10 Pages
      

ITEM 10. CERTIFICATION

        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.

        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.

Dated:   February 14, 2005

 
 
BIOTECHNOLOGY VALUE FUND, L.P.

 
 
By:
 
BVF Partners L.P., its general partner

 
 
 
 
By:
 
BVF Inc., its general partner

 
 
 
 
 
 
By:
 
/s/  MARK N. LAMPERT      
               
Mark N. Lampert
President

 
 
BIOTECHNOLOGY VALUE FUND II, L.P.

 
 
By:
 
BVF Partners L.P., its general partner

 
 
 
 
By:
 
BVF Inc., its general partner

 
 
 
 
 
 
By:
 
/s/  MARK N. LAMPERT      
               
Mark N. Lampert
President

 
 
BVF INVESTMENTS, L.L.C.

 
 
By:
 
BVF Partners L.P., its manager

 
 
 
 
By:
 
BVF Inc., its general partner

 
 
 
 
 
 
By:
 
/s/  MARK N. LAMPERT      
               
Mark N. Lampert
President

 
 
INVESTMENT 10, L.L.C.

 
 
By:
 
BVF Partners L.P., attorney-in-fact

 
 
 
 
By:
 
BVF Inc., its general partner

 
 
 
 
 
 
By:
 
/s/  MARK N. LAMPERT      
               
Mark N. Lampert
President

 
 
BVF PARTNERS L.P.

 
 
By:
 
BVF Inc., its general partner

 
 
 
 
 
 
By:
 
/s/  MARK N. LAMPERT      
               
Mark N. Lampert
President

 
 
BVF INC.

 
 
 
 
 
 
By:
 
/s/  MARK N. LAMPERT      
               
Mark N. Lampert
President