Anti-TFPI antibody variants with differential binding across PH range for improved pharmacokinetics
US9556280B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Mar 14, 2014 |
| Grant date | Jan 31, 2017 |
| Priority date | — |
| Expiry date | Jul 9, 2034 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07K2317/94
- WIPO fieldBiotechnology
- WIPO sectorChemistry
Abstract
Antibodies are disclosed that bind to and inhibit the anti-coagulant function of TFPI and have a lower affinity for TFPI at pH 6.0 than at pH 7.4. The lower affinity at pH 6 improves circulating half-life (T½) due to reduced target mediated clearance, a process by which an antibody/antigen complex is endocytosed and trafficked to the lysosome where both components are degraded. The lower affinity at pH 6.0 results in disruption of the complex prior to lysosome targeting and allows for re-circulation of the antibody. Specific modifications to antibody binding by histidine residue substitution are disclosed along with methods of use.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.