Compositions and methods for growth factor modulation

Patent metadata

Field	Value
Publication number	US-9758576-B2
Application number	US-201514795012-A
Country	US
Kind code	B2
Filing date	Jul 9, 2015
Priority date	May 6, 2013
Publication date	Sep 12, 2017
Grant date	Sep 12, 2017

Abstract

Provided herein are antibodies that bind growth factor prodomain complexes, for example, growth factor prodomain complexes that include GDF-8 growth factor and GDF-8 prodomain. Also included are antibodies that bind growth factor prodomain complexes that have been altered by proteolytic processing.

First claim

The invention claimed is:

1. 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 binds the GDF-8 prodomain of said GPC,
wherein the antibody or fragment thereof but 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,
wherein said antibody, or fragment thereof, prevents proteolytic cleavage between residues Arg 75 and Asp 76 of GDF-8 prodomain, and
wherein said antibody, or fragment thereof, inhibits the release of said mature GDF-8 growth factor from the GPC.

2. The antibody of claim 1 , wherein said antibody recognizes an epitope within the GDF-8 arm region of the GDF-8 prodomain set forth in SEQ ID NO: 77.

3. The antibody of claim 1 , 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 (SEQ ID NO: 70).

4. The antibody of claim 1 , wherein said antibody prevents the proteolytic cleavage by at least one metalloproteinase.

5. The antibody of claim 4 , wherein said metalloproteinase is mammalian tolloid-like 2 (mTLL2).

6. The antibody of claim 1 , wherein said GDF-8 prodomain has not been cleaved at a furin cleavage site.

7. The antibody of claim 1 , wherein said GDF-8 prodomain has been cleaved at a furin cleavage site.

8. The antibody of claim 7 , wherein said furin cleavage site is Arg-Ser-Arg-Arg set forth in SEQ ID NO: 76.

9. The antibody of claim 1 , wherein said antibody is an IgG antibody.

10. The antibody of claim 9 , wherein said IgG antibody is a human or humanized antibody.

Assignees

• Scholar Rock Inc

Inventors

• Schurpf Thomas
• Mahanthappa Nagesh K
• Straub Michelle Marie

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/02

  Immunomodulators · CPC title