Methods of increasing muscle mass or muscle strength using antibody inhibitors of GDF-8
View Patent ↗The disclosure provides novel antibodies against growth and differentiation factor-8 (GDF-8), including antibody fragments, which inhibit GDF-8 activity in vitro and in vivo. The disclosure also provides methods for diagnosing, preventing, or treating degenerative disorders of muscle, bone, or insulin metabolism.
1. A method of treating a patient suffering from a medical-disorder, wherein the patient would therapeutically benefit from an increase in mass or strength of muscle tissue, comprising: administering to a patient a therapeutically effective dose of an isolated antibody that specifically binds to amino acids 1-50 of the polypeptide of SEQ ID NO:15, wherein the antibody reduces GDF-8 activity associated with negative regulation of muscle mass, and wherein the antibody reduces one or more biological activities associated with a GDF-8 protein in the patient, relative to a patient not receiving the same antibody.
2. The method of claim 1 , wherein the antibody binds to the GDF-8 protein in the region from amino acid 1 to amino acid 25 of the polypeptide of SEQ ID NO:15.
3. The method of claim 1 , wherein the antibody binds the polypeptide of SEQ ID NO:5, wherein the antibody reduces GDF-8 activity associated with negative regulation of muscle mass.
4. The method of claim 1 , wherein the antibody binds the amino acid sequence Asp-Phe-Gly-Leu-Asp-Cys-Asp-Glu-His-Ser-Thr-Glu-Ser-Arg-Cys (SEQ ID NO:8).
5. The method of claim 1 , wherein the antibody binds the amino acid sequence Asp-Glu-His-Ser-Thr (SEQ ID NO:3).
6. The method of claim 1 , wherein the antibody recognizes the GDF-8 latent complex, GDF-8 in complex with follisatin, or GDF-8 in complex with a follistatin-related protein.
7. The method of claim 1 , wherein the antibody is produced by a cell having ATCC Deposit Designation Number PTA-4236.
8. The method of claim 1 , wherein the medical disorder is a muscular disorder, adipose tissue disorder, metabolic disorder, diabetes, or bone degenerative disorder.
9. The method of claim 1 , wherein the medical disorder is a muscular disorder.
10. The method of claim 1 , wherein the medical disorder is muscular dystrophy, muscle atrophy, muscle wasting syndrome, sarcopenia, or cachexia.
11. The method of claim 1 , wherein the medical disorder is muscular dystrophy.
12. The method of claim 1 , wherein the medical disorder is obesity, type 2 diabetes, or osteoporosis.
13. A method of increasing muscle mass in a mammal, said method comprising administering a therapeutically effective amount of an isolated antibody that specifically binds to amino acids 1-50 of the polypeptide of SEQ ID NO:15, wherein the antibody reduces GDF-8 activity associated with negative regulation of muscle mass to a mammal, thereby increasing muscle mass.
14. The method of claim 13 , wherein the antibody binds to the GDF-8 protein in the region from amino acid 1 to amino acid 25 of the polypeptide of SEQ ID NO:15.
15. The method of claim 13 , wherein the antibody binds the polypeptide of SEQ ID NO:5, wherein the antibody reduces GDF-8 activity associated with negative regulation of muscle mass.
16. The method of claim 13 , wherein the antibody binds the amino acid sequence Asp-Phe-Gly-Leu-Asp-Cys-Asp-Glu-His-Ser-Thr-Glu-Ser-Arg-Cys (SEQ ID NO:8).
17. The method of claim 13 , wherein the antibody binds the amino acid sequence Asp-Glu-His-Ser-Thr (SEQ ID NO:3).
18. The method of claim 13 , wherein the antibody recognizes the GDF-8 latent complex, GDF-8 in complex with follisatin, or GDF-8 in complex with a follistatin-related protein.
19. The method of claim 13 , wherein the antibody is produced by a cell having ATCC Deposit Designation Number PTA-4236.
20. A method of increasing muscle strength in a mammal comprising administering a therapeutically effective amount of an isolated antibody that specifically binds to amino acids 1-50 of the polypeptide of SEQ ID NO:15, wherein the antibody reduces GDF-8 activity associated with negative regulation of muscle mass to a mammal, thereby increasing muscle strength.
21. The method of claim 20 , wherein the antibody binds to the GDF-8 protein in the region from amino acid 1 to amino acid 25 of the polypeptide of SEQ ID NO:15.
22. The method of claim 20 , wherein the antibody binds the polypeptide of SEQ ID NO:5, wherein the antibody reduces GDF-8 activity associated with negative regulation of muscle mass.
23. The method of claim 20 , wherein the antibody binds the amino acid sequence Asp-Phe-Gly-Leu-Asp-Cys-Asp-Glu-His-Ser-Thr-Glu-Ser-Arg-Cys (SEQ ID NO:8).
24. The method of claim 20 , wherein the antibody binds the amino acid sequence Asp-Glu-His-Ser-Thr (SEQ ID NO:3).
25. The method of claim 20 , wherein the antibody recognizes the GDF-8 latent complex, GDF-8 in complex with follisatin, or GDF-8 in complex with a follistatin-related protein.
26. The method of claim 20 , wherein the antibody is produced by a cell having ATCC Deposit Designation Number PTA-4236.