USE OF AN FGF-21 COMPOUND AND A GLP-1 COMPOUND FOR THE TREATMENT OF OBESITY

• US 20110034373A1
• Filed: 07/30/2008
• Published: 02/10/2011
• Est. Priority Date: 08/03/2007
• Status: Abandoned Application

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Coskun, Tamer, Glaesner, Wolfgang
• Application Number:
  US12/668,475
• Publication Number:
  US 20110034373A1
• Time in Patent Office: Days
• US Class Current: 514/5.3
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention provides methods of lowering body weight by administering an FGF-21 compound in combination with a GLP-1 compound. In addition, the present invention also provides methods to treat obesity by administering an FGF-21 compound in combination with a GLP-1 compound. The present invention also discloses combinations useful in the methods of the present invention.

Claims

1-15. -15. (canceled)

16. A method of treating obesity comprising administering an FGF-21 compound in combination with a GLP-1 compound, wherein the FGF-21 compound is an FGF-21 analog selected from the group consisting of Cys¹¹⁸-Cys¹³⁴-FGF-21 (SEQ ID NO:

9), Cys¹¹⁸-Cys¹³⁴-Ala¹⁶⁷-FGF-21 (SEQ ID NO;

     10), Cys²¹-Cys³³-Ala¹⁶⁷-FGF-21 (SEQ ID NO;

     11), Cys²⁶-Cys¹²²-Ala¹⁶⁷-FGF-21 (SEQ ID NO;

     12), and Cys¹¹⁸-Cys¹³⁴-Ala¹²¹-Ala¹⁶⁷-FGF-21 (SEQ ID NO;

     13).

17. The method according to claim 16, wherein the FGF-21 analog is Cys¹¹⁸-Cys¹³⁴-Ala¹⁶⁷-FGF-21 (SEQ ID NO:

10).

18. The method according to claim 16, wherein the FGF-21 analog is Cys¹¹⁸-Cys¹³⁴-Ala¹²¹-Ala¹⁶⁷-FGF-21 (SEQ ID NO:

13).

19. The method according to claim 16, wherein the GLP-1 compound is a GLP-1 analog which comprises an amino acid sequence of SEQ ID NO:

14;

20. The method according to claim 19, wherein the GLP-1 analog comprises the amino acid sequence of Val⁸-Glu²²-GLP-1 (SEQ ID NO:

17).

21. The method according to claim 19, wherein the GLP-1 analog comprises the amino acid sequence of Val⁸-Glu²²-Ile³³-Lys³⁴-Gly³⁶-Pro³⁷-Ser³⁸-Ser³⁹-Gly⁴⁰-Ala⁴¹-Pro⁴²-Pro⁴³-Pro⁴⁴-Ser⁴⁵-GLP-1 (SEQ ID NO:

19).

22. The method according to claim 16, wherein the GLP-1 compound is a GLP-derivative.

23. The method according to claim 22, wherein the GLP-1 derivative comprises an amino acid sequence of SEQ ID NO:

20;

24. The method according to claim 16, wherein the GLP-1 compound is a GLP-1 fusion protein.

25. The method according to claim 24, wherein the GLP-1 fusion protein comprises a GLP-1 peptide and an Fc portion of an immunoglobulin, wherein the GLP-1 peptide comprises an amino acid sequence of SEQ ID NO:

22;

26. The method according to claim 25, wherein the GLP-1 fusion protein further comprises a linker, wherein the linker comprises an amino acid sequence selected from the group consisting of SEQ ID NO:

6, SEQ ID NO;

7, and SEQ ID NO;

8.

27. A method of lowering body weight comprising administering an FGF-21 compound in combination with a GLP-1 compound, wherein the FGF-21 compound is an FGF-21 analog selected from the group consisting of Cys¹¹⁸-Cys¹³⁴-FGF-21 (SEQ ID NO:

9), Cys¹¹⁸-Cys¹³⁴-Ala¹⁶⁷-FGF-21 (SEQ ID NO;

     10), Cys²¹-Cys³³-Ala¹⁶⁷-FGF-21 (SEQ ID NO;

     11), Cys²⁶-Cys¹²²-Ala¹⁶⁷-FGF-21 (SEQ ID NO;

     12), and Cys¹¹⁸-Cys¹³⁴-Ala¹²¹-Ala¹⁶⁷-FGF-21 (SEQ ID NO;

     13).

28. The method according to claim 27, wherein the FGF-21 analog is Cys¹¹⁸-Cys¹³⁴-Ala¹⁶⁷-FGF-21 (SEQ ID NO:

10).

29. The method according to claim 27, wherein the FGF-21 analog is Cys¹¹⁸-Cys¹³⁴-Ala¹²¹-Ala¹⁶⁷-FGF-21 (SEQ ID NO:

13).

30. The method according to claim 27, wherein the GLP-1 compound is a GLP-1 analog which comprises an amino acid sequence of SEQ ID NO:

14;

31. The method according to claim 30, wherein the GLP-1 analog comprises the amino acid sequence of Val⁸-Glu²²-GLP-1 (SEQ ID NO:

17).

32. The method according to claim 30, wherein the GLP-1 analog comprises the amino acid sequence of Val⁸-Glu²²-Ile³³-Lys³⁴-Gly³⁶-Pro³⁷-Ser³⁸-Ser³⁹-Gly⁴⁰-Ala⁴¹-Pro⁴²-Pro⁴³-Pro⁴⁴-Ser⁴⁵-GLP-1 (SEQ ID NO:

19).

33. The method according to claim 27, wherein the GLP-1 compound is a GLP-1 derivative.

34. The method according to claim 33, wherein the GLP-1 derivative comprises an amino acid sequence of SEQ ID NO:

20;

35. The method according to claim 27, wherein the GLP-1 compound is a GLP-1 fusion protein.

36. The method according to claim 35, wherein the GLP-1 fusion protein comprises a GLP-1 peptide and an Fc portion of an immunoglobulin wherein the GLP-1 peptide comprises an amino acid sequence of SEQ ID NO:

22;

37. The method according to claim 36, wherein the GLP-1 fusion protein further comprises a linker, wherein the linker comprises an amino acid sequence selected from the group consisting of SEQ ID NO:

6, SEQ ID NO;

7, and SEQ ID NO;

8.