Covalently dimerized bivalent binding agents
US8987417B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Nov 28, 2011 |
| Grant date | Mar 24, 2015 |
| Priority date | — |
| Expiry date | Nov 28, 2031 |
Classification
- Technology area (CPC G)Physics
- CPC primaryG01N2333/71
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
The present invention addresses limitations of prior art receptor-based traps through a methodology called the clamp/click/cleave (CCC) approach. Two fusion proteins each comprising a binding domain fused to a coiled-coil are non-covalently dimerized through the coiled-coil (clamp), and the dimer so formed is stabilized by a covalent disulphide bond (click) between cysteine residues located on the fusion proteins between the binding domains and coiled-coils. Once the disulphide bond has formed, the coiled-coils are subsequently removed (cleave) by cleaving the fusions proteins at cleavage sites located between the cysteine residues and the coiled-coils to provide the covalently dimerized bivalent binding agent of the present invention. Such binding agents are useful in the treatment and diagnosis of disease states characterized by production and/or overexpression of a ligand to which the binding domains bind. The invention is particularly useful for covalently dimerized receptor-based ligand traps where the binding domains are receptor ligand-binding domains, such as those of TGF-β receptors.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.