Anti-pro/latent-Myostatin antibodies and uses thereof
Aspects of the present disclosure relate to antibodies that specifically bind proMyostatin and/or latent Myostatin and uses thereof.
1. An isolated antibody that specifically binds pro/latent myostatin, comprising a heavy chain comprising an amino acid sequence of SEQ ID NO:50 and a light chain comprising an amino acid sequence of SEQ ID NO:51.
2. The isolated antibody of claim 1 , wherein the antibody inhibits proteolytic formation of mature myostatin by tolloid protease.
3. The isolated antibody of claim 2 , wherein the antibody inhibits proteolytic formation of mature myostatin by tolloid protease with an IC50 of less than 1 μM.
4. The isolated antibody of claim 1 , wherein the antibody is cross-reactive with human pro/latent-myostatin and murine pro/latent-myostatin.
5. The isolated antibody of claim 1 , wherein the antibody does not bind mature myostatin.
6. The isolated antibody of claim 1 , wherein the antibody does not bind GDF11 or Activin A.
7. A method of treating a subject having, or at risk of developing, a myopathy, muscle atrophy, and/or metabolic disorder, the method comprising administering to the subject the antibody of claim 1 in an amount effective to treat the myopathy, muscle atrophy, and/or metabolic disorder.
8. The method of claim 7 , wherein the antibody is administered in an amount effective to increase muscle mass, enhance force generation, and/or prevent muscle loss in the subject.
9. The method of claim 7 , wherein the amount is between about 0.3 and 30 mg/kg per dose.
10. The method of claim 7 , wherein the method comprises intravenous administration or subcutaneous administration.
11. A pharmaceutical composition comprising an antibody having a heavy chain comprising an amino acid sequence of SEQ ID NO:50 and a light chain comprising an amino acid sequence of SEQ ID NO:51, and a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier comprises histidine.