Methods of Improving or Accelerating Physical Recovery After Surgery for Hip Fracture

Abstract

The disclosure relates to novel uses and regimens for accelerating/improving physical recovery in a patient with disuse atrophy triggered by reduced mobility due to a hip fracture and consequent major surgery, which employ a therapeutically effective amount of a myostatin antagonist, e.g., a myostatin binding molecule, e.g., a myostatin antibody or an ActRII receptor binding molecule, an ActRII receptor antibody, such as the bimagrumab antibody.

1 . A method of improving muscle mass and function in a patient with disuse atrophy, triggered by reduced mobility due to a hip fracture, comprising administering a therapeutically effective amount of an antibody or antigen binding fragment thereof that binds to human ActRIIB to a patient in need thereof, wherein said antibody or antigen binding fragment thereof comprises:
 i) an immunoglobulin V H  domain comprising the amino acid sequence set forth as SEQ ID NO:107 and an immunoglobulin V L  domain comprising the amino acid sequence set forth as SEQ ID NO:93;   ii) an immunoglobulin V H  domain comprising, in sequence, a complementarity determining region (CDR) 1 comprising the amino acid sequence set forth as SEQ ID NO:9, a CDR2 comprising the amino acid sequence set forth as SEQ ID NO:23, and a CDR3 comprising the amino acid sequence set forth as SEQ ID NO:37, and an immunoglobulin V L  domain comprising, in sequence, a CDR1 comprising the amino acid sequence set forth as SEQ ID NO:51, a CDR2 comprising the amino acid sequence set forth as SEQ ID NO:65 and a CDR3 comprising the amino acid sequence set forth as SEQ ID NO:79.   
     
     
         2 . A method of treating a patient having disuse atrophy triggered by reduced mobility due to a hip fracture and consequent major surgery for hip fracture repair, comprising administering a therapeutically effective amount of an antibody or antigen binding fragment thereof that binds to human ActRIIB to a patient in need thereof, wherein said antibody or antigen binding fragment thereof comprises:
 i) an immunoglobulin V H  domain comprising the amino acid sequence set forth as SEQ ID NO:107 and an immunoglobulin V L  domain comprising the amino acid sequence set forth as SEQ ID NO:93;   ii) an immunoglobulin V H  domain comprising, in sequence, a complementarity determining region (CDR) 1 comprising the amino acid sequence set forth as SEQ ID NO:9, a CDR2 comprising the amino acid sequence set forth as SEQ ID NO:23, and a CDR3 comprising the amino acid sequence set forth as SEQ ID NO:37, and an immunoglobulin V L  domain comprising, in sequence, a CDR1 comprising the amino acid sequence set forth as SEQ ID NO:51, a CDR2 comprising the amino acid sequence set forth as SEQ ID NO:65 and a CDR3 comprising the amino acid sequence set forth as SEQ ID NO:79.   
     
     
         3 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof has a K D  of about 1 pM to about 100 pM, as measured by a biosensor system. 
     
     
         4 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is a Fab, Fab′, F(ab′) 2 , Fv, or a single chain Fv. 
     
     
         5 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is a human or humanized monoclonal antibody. 
     
     
         6 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof binds to an epitope of human ActRIIB comprising the amino acid sequence set forth as SEQ ID NO:182. 
     
     
         7 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is bimagrumab. 
     
     
         8 . The method according to  claim 7 , wherein the antibody or antigen binding fragment thereof is administered to the patient at a dose of about 70 mg or about 210 mg or about 700 mg. 
     
     
         9 . The method according to  claim 8 , wherein the antibody or antigen binding fragment thereof is administered to the patient intravenously. 
     
     
         10 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is administered to the patient subcutaneously. 
     
     
         11 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is administered to the patient every four weeks. 
     
     
         12 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is comprised in a lyophilized pharmaceutical formulation. 
     
     
         13 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is comprised in a liquid pharmaceutical formulation. 
     
     
         14 . The method according to  claim 13 , wherein the formulation is disposed within a pre-filled syringe, vial, injection pen, or autoinjector. 
     
     
         15 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is administered to the patient for at least 3 months. 
     
     
         16 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is administered to the patient for about 6 months. 
     
     
         17 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is administered to the patient for up to 12 months. 
     
     
         18 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is comprised in a dosage unit form suitable for intravenous administration. 
     
     
         19 . The method according to  claim 1 , wherein the dosage unit form contains an aqueous pharmaceutical composition disposed therein. 
     
     
         20 . The method according to  claim 14 , wherein said formulation comprises a pharmaceutically acceptable carrier and an excipient selected from an anti-oxidant, an isotonic agent, a surfactant, and a preservative.