Compositions and methods for growth factor modulation

Abstract

Provided herein are proteins, antibodies, assays and methods useful for modulating growth factor levels and/or activities. In some embodiments, such growth factors are members of the TGF-β superfamily of proteins.

1 .- 11 . (canceled) 
     
     
         12 . An isolated monoclonal antibody, or a fragment thereof, that binds a growth factor prodomain complex (GPC),
 wherein said GPC comprises a GDF-8 growth factor and a GDF-8 prodomain (SEQ ID NO: 70),   wherein the antibody or fragment thereof does not bind a mature GDF-8 growth factor, a mature GDF-11 growth factor, a GDF-11 prodomain or a complex comprising a GDF-11 prodomain and a GDF-11 growth factor, and   wherein said antibody, or fragment thereof, inhibits the release of said mature GDF-8 growth factor from the GPC.   
     
     
         13 . The antibody of  claim 12 , wherein said prodomain has not been cleaved at the BMP/tolloid cleavage site between residues Arg 75 and Asp 76 of the GDF-8 prodomain. 
     
     
         14 . The antibody of  claim 12 , wherein said antibody is an IgG antibody. 
     
     
         15 . The antibody of  claim 14 , wherein said IgG antibody is a human or humanized antibody. 
     
     
         16 . The antibody of  claim 12 , wherein said antibody prevents the proteolytic cleavage by at least one metalloproteinase. 
     
     
         17 . The antibody of  claim 16 , wherein said metalloproteinase is mammalian tolloid-like 2 (mTLL2). 
     
     
         18 . The antibody of  claim 12 , wherein said antibody recognizes an epitope within the GDF-8 arm region of the GDF-8 prodomain set forth in SEQ ID NO: 77. 
     
     
         19 . The antibody of  claim 12 , wherein said GDF-8 prodomain has not been cleaved at a furin cleavage site. 
     
     
         20 . The antibody of  claim 12 , wherein said GDF-8 prodomain has been cleaved at a furin cleavage site. 
     
     
         21 . The antibody of  claim 20 , wherein said furin cleavage site is Arg-Ser-Arg-Arg set forth in SEQ ID NO: 76.