METHODS FOR INHIBITING MYOSTATIN ACTIVATION BY ADMINISTERING ANTI-PRO/LATENT MYOSTATIN ANTIBODIES
The present invention relates to antibodies that specifically bind pro-myostatin and/or latent myostatin, and methods and uses thereof.
1 .- 22 . (canceled)
23 . A method of treating a subject having, or at risk of developing, a muscular dystrophy, the method comprising administering to the subject an effective amount of an antibody or antigen-binding fragment thereof,
wherein the antibody or antigen-binding fragment thereof comprises any one of the following:
i) a heavy chain sequence that is at least 95% identical to SEQ ID NO: 50 and a light chain sequence that is at least 95% identical to SEQ ID NO: 51;
ii) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO: 25 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO: 31;
iii) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO: 73 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO: 74;
iv) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO: 78 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO: 79; or
v) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO: 83 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO: 84.
24 . The method of claim 23 , wherein the effective amount is sufficient to prevent muscle loss or muscle atrophy.
25 . The method of claim 23 , wherein the effective amount is sufficient to cause two or more of the following in a subject:
a) an increase muscle mass and/or muscle function;
b) a decrease in ratio of adipose-to-muscle tissue in the subject;
c) a decrease in intramuscular fat infiltration in the subject; and
d) prevention of muscle loss or atrophy in a subject.
26 . The method of claim 23 , wherein the antibody or antigen-binding fragment thereof inhibits activation of mature myostatin by tolloid protease with an IC50 of less than 1 μM.
27 . The method of claim 23 , wherein the antibody or antigen-binding fragment thereof comprises an IgG4 constant domain.
28 . The method of claim 23 , wherein the antibody or antigen-binding fragment thereof is administered intravenously or subcutaneously.
29 . The method of claim 23 , wherein the subject is treated with one or more additional therapies.
30 . The method of claim 23 , wherein the muscular dystrophy is Duchenne's muscular dystrophy, Becker's muscular dystrophy, facioscapulohumeral (FSH) muscular dystrophy, or Limb-Girdle muscular dystrophy.
31 . The method of claim 23 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain sequence comprising SEQ ID NO: 50 and a light chain sequence comprising SEQ ID NO: 51.
32 . A method of treating a subject having osteogenesis imperfecta, the method comprising administering to the subject an effective amount of an antibody or antigen-binding fragment thereof,
wherein the antibody or antigen-binding fragment thereof comprises any one of the following:
i) a heavy chain sequence that is at least 95% identical to SEQ ID NO: 50 and a light chain sequence that is at least 95% identical to SEQ ID NO: 51;
ii) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO: 25 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO: 31;
iii) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO: 73 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO: 74;
iv) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO: 78 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO: 79; or
v) a heavy chain variable region sequence that is at least 95% identical to SEQ ID NO: 83 and a light chain variable region sequence that is at least 95% identical to SEQ ID NO: 84.
33 . The method of claim 32 , wherein the effective amount is sufficient to prevent muscle loss or muscle atrophy.
34 . The method of claim 32 , wherein the effective amount is sufficient to cause two or more of the following in a subject:
a) an increase muscle mass and/or muscle function;
b) a decrease in ratio of adipose-to-muscle tissue in the subject;
c) a decrease in intramuscular fat infiltration in the subject; and
d) prevention of muscle loss or atrophy in a subject.
35 . The method of claim 32 , wherein the antibody or antigen-binding fragment thereof inhibits activation of mature myostatin by tolloid protease with an IC50 of less than 1 μM.
36 . The method of claim 32 , wherein the antibody or antigen-binding fragment thereof comprises an IgG4 constant domain.
37 . The method of claim 32 , wherein the antibody or antigen-binding fragment thereof is administered intravenously or subcutaneously.
38 . The method of claim 32 , wherein the subject is treated with one or more additional therapies.
39 . The method of claim 32 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain sequence comprising SEQ ID NO: 50 and a light chain sequence comprising SEQ ID NO: 51.