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 .- 47 . (canceled) 
     
     
         48 . An isolated antibody that binds a protein complex, the protein complex comprising:
 a) a glycoprotein A repetitions predominant (GARP);   b) human transforming growth factor (TGF)-β1; and   c) human TGF-β1 latency-associated peptide (LAP);   wherein the antibody binds the protein complex but does not bind free human TGF-β1, free human TGF-β1 LAP, or free GARP; and,   wherein the GARP is human leucine rich repeat containing 32 (LRRC32) or human leucine rich repeat containing 33 (LRRC33).   
     
     
         49 . The antibody of  claim 48 , wherein the antibody binds a GARP epitope present in the protein complex. 
     
     
         50 . The antibody of  claim 48 , wherein the antibody binds an epitope formed by combining regions or portions of two or more of the components selected from the group consisting of:
 TGF-β1 growth factor prodomain complex (GPC),   GPC modulatory factor,   growth factor receiving cell,   growth factor receiving receptor,   TGF-β1 LAP,   TGF-β1 fastener region,   TGF-β1 furin cleavage site,   TGF-β1 arm region,   TGF-β1 fingers region,   TGF-β1 LTBP binding domain,   TGF-β1 fibrillin binding domain,   TGF-β1 glycoprotein A repetitions predominant (GARP) binding domain,   TGF-β1 latency lasso,   TGF-β1 alpha 1 region,   TGF-β1 RGD sequence,   TGF-β1 bowtie region,   extracellular matrix, and   cellular matrix.   
     
     
         51 . The antibody of  claim 50 , wherein the epitope is a combinatorial epitope, said combinatorial epitope formed between said GARP and said TGF-β1 GPC. 
     
     
         52 . The antibody of  claim 48 , wherein the GARP has an amino acid sequence selected from the group consisting of: SEQ ID NOs: 158-161. 
     
     
         53 . The antibody of  claim 48 , wherein the antibody is a human or humanized antibody or an antigen-binding portion thereof. 
     
     
         54 . The antibody of  claim 48 , wherein the antibody is an inhibitory antibody. 
     
     
         55 . A pharmaceutical composition comprising the antibody of  claim 48  and at least one pharmaceutically acceptable excipient.