Anti-FLT-1 Antibodies in Treating Duchenne Muscular Dystrophy

Abstract

The present invention provides, among other things, methods and compositions for treating muscular dystrophy, in particular, Duchenne muscular dystrophy (DMD). In some embodiments, a method according to the present invention includes administering to an individual who is suffering from or susceptible to DMD an effective amount of an anti-Flt-1 antibody, or antigen binding fragment thereof, such that at least one symptom or feature of DMD is reduced in intensity, severity, or frequency, or has delayed onset.

1 . A method of treating Duchenne Muscular Dystrophy (DMD) comprising administering to an individual who is suffering from or susceptible to DMD an effective amount of an anti-Flt-1 antibody, or an antigen binding fragment thereof, such that at least one symptom or feature of DMD is reduced in intensity, severity, or frequency, or has delayed onset. 
     
     
         2 . The method of  claim 1 , wherein the anti-Flt-1 antibody, or an antigen binding fragment thereof, is characterized with an ability to bind human Flt-1 at an affinity greater than 10 −9 M in a surface plasmon resonance binding assay. 
     
     
         3 - 4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the anti-Flt-1 antibody, or an antigen binding fragment thereof, is characterized with an IC 50  below 100 pM in a competition assay with human Flt-1. 
     
     
         6 - 7 . (canceled) 
     
     
         8 . The method of  claim 5 , wherein the competition assay is inhibition of binding of VEGF to human Flt-1. 
     
     
         9 . The method of  claim 5 , wherein the competition assay is inhibition of binding of PLGF to human Flt-1. 
     
     
         10 . The method of  claim 1 , wherein the anti-Flt-1 antibody, or an antigen binding fragment thereof, does not bind to VEGFR2 and/or VEGFR3. 
     
     
         11 . The method of  claim 1 , wherein the anti-Flt-1 antibody, or an antigen binding fragment thereof, does not bind to a mouse or monkey Flt-1. 
     
     
         12 . The method of  claim 1 , wherein the anti-Flt-1 antibody, or an antigen binding fragment thereof, binds to a mouse and/or monkey Flt-1. 
     
     
         13 . The method of  claim 1 , wherein the anti-Flt-1 antibody, or an antigen binding fragment thereof, is selected from the group consisting of IgG, F(ab′) 2 , F(ab) 2 , Fab′, Fab, ScFv s, diabodies, triabodies and tetrabodies. 
     
     
         14 . The method of  claim 13 , wherein the anti-Flt-1 antibody, or an antigen binding fragment thereof, is IgG. 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 14 , wherein the anti-Flt-1 antibody, or an antigen binding fragment thereof, is a monoclonal antibody. 
     
     
         17 - 20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the anti-Flt-1 antibody, or an antigen binding fragment thereof, is administered parenterally. 
     
     
         22 - 26 . (canceled) 
     
     
         27 . The method of  claim 1 , wherein the anti-Flt-1 antibody, or an antigen binding fragment thereof, is delivered to one or more skeletal muscles selected from Table 1. 
     
     
         28 - 30 . (canceled) 
     
     
         31 . The method of  claim 1 , wherein the administration of the anti-Flt-1 antibody, or an antigen binding fragment thereof, results in muscle regeneration, fibrosis reduction, increased stability, increased muscle strength, increased flexibility, increased range of motion, increased stamina, reduced fatiguability, increased blood flow, improved cognition, improved pulmonary function, and/or inflammation inhibition. 
     
     
         32 . (canceled) 
     
     
         33 . An anti-Flt-1 antibody, or an antigen binding fragment thereof, having a binding affinity to human Flt-1 greater than 10 −9 M in a surface plasmon resonance binding assay. 
     
     
         34 - 35 . (canceled) 
     
     
         36 . The anti-Flt-1 antibody, or an antigen binding fragment thereof, of  claim 33 , wherein the anti-Flt-1 antibody, or an antigen binding fragment thereof, is further characterized with an IC 50  below 100 pM for inhibition of binding of VEGF and/or PLGF to human Flt-1 in a competition assay. 
     
     
         37 - 38 . (canceled) 
     
     
         39 . The anti-Flt-1 antibody, or an antigen binding fragment thereof, of  claim 33 , wherein the anti-Flt-1 antibody, or an antigen binding fragment thereof, does not bind to VEGFR2 and/or VEGFR3. 
     
     
         40 . The anti-Flt-1 antibody, or an antigen binding fragment thereof, of  claim 33 , wherein the anti-Flt-1 antibody, or an antigen binding fragment thereof, does not bind a mouse or monkey Flt-1. 
     
     
         41 . The anti-Flt-1 antibody, or an antigen binding fragment thereof, of  claim 33 , wherein the anti-Flt-1 antibody, or an antigen binding fragment thereof, binds to a mouse and/or monkey Flt-1. 
     
     
         42 . A pharmaceutical composition comprising an anti-Flt-1 antibody, or an antigen binding fragment thereof, of  claim 33 , and a pharmaceutically acceptable carrier.