Use of Acrp30 globular head to promote increases in muscle mass and muscle differentiation

• US 7,405,193 B2
• Filed: 05/22/2001
• Issued: 07/29/2008
• Est. Priority Date: 05/31/2000
• Status: Expired due to Fees

• Current Assignee: Serono Genetics Institute S.A. (Merck & Co., Inc.), Whitehead Institute for Biomedical Research
• Original Assignee: Serono Genetics Institute S.A. (Merck & Co., Inc.)
• Inventors: Bihain, Bernard, Lodish, Harvey, Fruebis, Joachim, Tsao, Tsu-Shuen
• Primary Examiner(s): Kemmerer; Elizabeth C.
• Assistant Examiner(s): BORGEEST, CHRISTINA M
• Application Number:
  US10/296,865
• Publication Number:
  US 20060035824A1
• Time in Patent Office: 2,625 Days
• Field of Search: None
• US Class Current: 514/9.4
• CPC Class Codes: A61K 38/2264 Obesity-gene products, e.g. leptin
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: C07K 14/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]

Abstract

The present invention relates to the field of muscle research, in particular to the discovery of a compound effective for increasing muscle mass, muscle cell differentiation, and oxidation of free fatty acids in muscle, useful in methods of treating muscle-related diseases and disorders as well as for augmenting muscle mass in general. The muscle-related diseases or disorders envisaged to be treated by the methods of the invention include, but are not limited to, muscular dystrophy, and other conditions resulting in muscle atrophy or muscle wasting.

Claims

1. A method of accelerating skeletal muscle cell differentiation, comprising contacting skeletal muscle cells in vitro with gOBG3 polypeptides consisting of:

amino acids 101-244 of SEQ ID NO;

6, amino acids 108-244 of SEQ ID NO;

6, amino acids 104-247 of SEQ ID NOs;

2 or 4, or amino acids 111-247 of SEQ ID NOs;

2 or 4, or variants thereof comprising polyethylene glycol conjugated to gOBG3 polypeptides consisting of;

amino acids 101-244 of SEQ ID NO;

6, amino acids 108-244 of SEQ ID NO;

6, amino acids 104-247 of SEQ ID NOs;

2 or 4, or amino acids 111-247 of SEQ ID NOs;

2 or 4, wherein said gOBG3 accelerates the differentiation of said cells.

18. The method according to claim 1, wherein said gOBG3 polypeptides consist of amino acids 101-244 of SEQ ID NO:

6.

19. The method according to claim 1, wherein said gOBG3 polypeptides consist of amino acids 108-244 of SEQ ID NO:

6.

20. The method according to claim 1, wherein said gOBG3 polypeptides consist of amino acids 104-247 of SEQ ID NO:

2.

21. The method according to claim 1, wherein said gOBG3 variant comprises polyethylene glycol conjugated to gOBG3 polypeptides consisting of amino acids 101-244 of SEQ ID NO:

6.

22. The method according to claim 1, wherein said gOBG3 variant comprises polyethylene glycol conjugated to gOBG3 polypeptides consisting of amino acids 108-244 of SEQ ID NO:

6.

23. The method according to claim 1, wherein said gOBG3 variant comprises polyethylene glycol conjugated to gOBG3 polypeptides consisting of amino acids 104-247 of SEQ ID NO:

2.

24. The method according to claim 1, wherein said gOBG3 variant comprises polyethylene glycol conjugated to gOBG3 polypeptides consisting of amino acids 111-247 of SEQ ID NO:

2.

2. A method of accelerating skeletal muscle cell realignment in relation to other skeletal muscle cells in vitro, comprising contacting skeletal muscle cells in vitro with gOBG3 polypeptides consisting of:

amino acids 101-244 of SEQ ID NO;

6, amino acids 108-244 of SEQ ID NO;

6, amino acids 104-247 of SEQ ID NOs;

2or 4, or amino acids 111-247 of SEQ ID NOs;

2 or 4, or variants thereof comprising polyethylene glycol conjugated to gOBG3 polypeptides consisting of;

amino acids 101-244 of SEQ ID NO;

6, amino acids 108-244 of SEQ ID NO;

6, amino acids 104-247 of SEQ ID NOs;

2 or 4, or amino acids 111-247 of SEQ ID NOs;

2 or 4 in an amount sufficient to accelerate the realignment of said skeletal muscle cells in relation to each other.

25. The method according to claim 2, wherein said gOBG3 polypeptides consist of amino acids 101-244 of SEQ ID NO:

6.

26. The method according to claim 2, wherein said gOBG3 polypeptides consist of amino acids 108-244 of SEQ ID NO:

6.

27. The method according to claim 2, wherein said gOBG3 polypeptides consist of amino acids 104-247 of SEQ ID NO:

2.

28. The method according to claim 2, wherein said gOBG3 polypeptides consist of amino acids 111-247 of SEQ ID NO:

2.

29. The method according to claim 2, wherein said gOBG3 variant comprises polyethylene glycol conjugated to gOBG3 polypeptides consisting of amino acids 101-244 of SEQ ID NO:

6.

30. The method according to claim 2, wherein said gOBG3 variant comprises polyethylene glycol conjugated to gOBG3 polypeptides consisting of amino acids 108-244 of SEQ ID NO:

6.

31. The method according to claim 2, wherein said gOBG3 variant comprises polyethylene glycol conjugated to gOBG3 polypeptides consisting of amino acids 104-247 of SEQ ID NO:

2.

32. The method according to claim 2, wherein said gOBG3 polypeptides consist of amino acids 111-247 of SEQ ID NO:

2.

3. A method of treating skeletal muscle cell disorders selected from the group consisting of muscle-related recovery after injuries, muscle-related recovery after surgery, and muscle wasting in an individual, comprising diagnosing an individual as having a skeletal muscle cell disorder selected from the group consisting of muscle-related recovery after injuries, muscle-related recovery after surgery, and muscle wasting and administering to said diagnosed individual an amount of gOBG3 polypeptide consisting of:

amino acids 101-244 of SEQ ID NO;

6, amino acids 108-244 of SEQ ID NO;

6, amino acids 104-247 of SEQ ID NOs;

2 or 4, amino acids 111-247 of SEQ ID NOs;

2 or 4, or variants thereof comprising polyethylene glycol conjugated to gOBG3 polypeptides consisting of;

amino acids 101-244 of SEQ ID NO;

6, amino acids 108-244 of SEQ ID NO;

6, amino acids 104-247 of SEQ ID NOs;

2 or 4, or amino acids 111-247 of SEQ ID NOs;

2 or 4 sufficient to accelerate the reorganization and alignment of said cells in relation to each other and treat said disorder.

33. The method according to claim 3, wherein said gOBG3 polypeptides consist of amino acids 101-244 of SEQ ID NO:

6.

34. The method according to claim 3, wherein said gOBG3 polyethylene consist of amino acids 108-244 of SEQ ID NO:

6.

35. The method according to claim 3, wherein said gOBG3 variant comprises polyethylene glycol conjugated to gOBG3 polypeptides consisting of amino acids 101-244 of SEQ ID NO:

6.

36. The method according to claim 3, wherein said gOBG3 variant comprises polyethylene glycol conjugated to gOBG3 polypeptides consisting of amino acids 108-244 of SEQ ID NO:

6.

4. A method of treating skeletal muscle injury comprising selecting an individual having a skeletal muscle injury and administering to an individual in need thereof a therapeutically effective dose of gOBG3 polypeptide, said gOBG3 polypeptide consisting of:

amino acids 101-244 of SEQ ID NO;

6, amino acids 108-244 of SEQ ID NO;

6, amino acids 104-247 of SEQ ID NOs;

2 or 4, or amino acids 111-247 of SEQ ID NOs;

2 or 4, or variants thereof comprising polyethyleneglycol conjugated to gOBG3 polypeptides consisting of;

amino acids 101-244 of SEQ ID NO;

6, amino acids 108-244 of SEQ ID NO;

6, amino acids 104-247 of SEQ ID NOs;

2 or 4, or amino acids 111-247 of SEQ ID NOs;

2 or 4, wherein said therapeutically effective dose is sufficient for treating said skeletal muscle injury.

5. The method according to claim 4, wherein said skeletal muscle injury is trauma.

6. The method according to claim 5, wherein said trauma is due to accident, surgery or over-exercise.

7. The method according to claim 6, wherein said trauma is surgery.

8. The method according to claim 6, wherein said trauma is due to accident.

9. The method according to claim 4, wherein said gOBG3 polypeptides consist of amino acids 101-244 of SEQ ID NO:

6.

10. The method according to claim 4, wherein said gOBG3 polypeptides consist of amino acids 108-244 of SEQ ID NO:

6.

11. The method according to claim 4, wherein said gOBG3 variant comprises polyethylene glycol conjugated to gOBG3 polypeptides consisting of amino acids 101-244 of SEQ ID NO:

6.

12. The method according to claim 4, wherein said gOBG3 variant comprises polyethylene glycol conjugated to gOBG3 polypeptides consisting of amino acids 108-244 of SEQ ID NO:

6.

13. A method of treating a skeletal muscle disorder comprising diagnosing an individual as having a skeletal muscle disorder and administering to said diagnosed individual a therapeutically effective dose of gOBG3 polypeptide, said gOBG3 polypeptide consisting of:

amino acids 101-244 of SEQ ID NO;

6, amino acids 108-244 of SEQ ID NO;

6, amino acids 104-247 of SEQ ID NOs;

2 or 4, amino acids 111-247 of SEQ ID NOs;

2 or 4, orvariants thereof comprising polyethylene glycol conjugated to gOBG3 polypeptides consisting of;

amino acids 101-244 of SEQ ID NO;

6, amino acids 108-244 of SEQ ID NO;

6, amino acids 104-247 of SEQ ID NOs;

2 or 4, or amino acids 111-247 of SEQ ID NOs;

2 or 4, wherein said effective dose is sufficient for treating said skeletal muscle disorder.

14. The method according to claim 13, wherein said gOBG3 polypeptides consist of amino acids 101-244 of SEQ ID NO:

6.

15. The method according to claim 13, wherein said gO13G3 polypeptides consist of amino acids 108-244 of SEQ ID NO:

6.

16. The method according to claim 13, wherein said gOBG3 variant comprises polyethylene glycol conjugated to gOBG3 polypeptides consisting of amino acids 101-244 of SEQ ID NO:

6.

17. The method according to claim 13, wherein said gOBG3 variant comprises polyethylene glycol conjugated to gOBG3 polypeptides consisting of amino acids 108-244 of SEQ ID NO:

6.