Antibody against a human ADAM protease
US7960513B2 · kind B2 · utility
Assignees
Inventors
Key dates
| Filing date | Dec 19, 2005 |
| Grant date | Jun 14, 2011 |
| Priority date | — |
| Expiry date | Dec 28, 2026 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC12N9/6489
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
Elucidation of the crystal structure of an ADAM10 substrate-recognition and proteinase-positioning module comprising the protein cysteine-rich and disintegrin domains, and detailed functional analysis revealed that an acidic pocket within the cysteine-rich domain forms a substrate-recognition site. The binding of this pocket to receptor/ligand complexes facilitates effective ligand cleavage, which is prevented when critical residues within the pocket are changed. This provides use of the surface pocket within the extracellular domain of ADAM10, and the corresponding structure in related proteases such as ADAM17, as a target for structure-based computational and high-throughput screens for small-molecule substrate-specific inhibitors or monoclonal antibodies that inhibit ADAM protease cleavage of ephrins and other ADAM10 or ADAM17 substrates. These inhibitors will be useful in therapeutic intervention of tumour development, invasion and metastasis and other diseases which involve the activity of the ADAM10 and ADAM17 proteases, such as inflammation, cardio-vascular disease, arthritis and other auto-immune diseases.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.