Compositions and methods for growth factor modulation
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. An antibody that binds to a protein complex, said protein complex comprising:
a. glycoprotein-A repetitions predominant protein (GARP) comprising the amino acid sequence of SEQ ID NO: 159, and
b. a growth factor prodomain complex (GPC) comprising human TGF-β1 growth factor and human TGF-β1 LAP;
wherein said antibody binds a GARP epitope of the protein complex, but does not bind free GARP.
2. The antibody of claim 1 , wherein said antibody is a TGF-β1 inhibiting antibody.
3. The inhibiting antibody of claim 2 , wherein said inhibiting antibody is a humanized antibody.
4. The inhibiting antibody of claim 2 , wherein said inhibiting antibody is a monoclonal antibody.
5. The inhibiting antibody of claim 2 , wherein said inhibiting antibody is a multispecific antibody.
6. The multispecific antibody of claim 5 comprising a bispecific antibody.
7. The inhibiting antibody of claim 2 , wherein said inhibiting antibody is an antibody fragment.
8. The inhibiting antibody of claim 7 , wherein said antibody fragment is selected from the group consisting of a Fab, a Fab′, a F(ab′) 2 , a Fv fragment, a diabody, a linear antibody, and a single-chain antibody molecule.
9. The inhibiting antibody of claim 2 comprising an antibody mimetic.
10. The inhibiting antibody of claim 9 , wherein the antibody mimetic is selected from the group consisting of a monobody, an affibody, an affilin, an affitin, an anticalin, an avimer, a centyrin, a darpin, and a fynomer.