Mutant plasminogen activator-inhibitor type 1 (PAI-1) and uses thereof
US6103498A · kind A · utility
Assignee
Inventors
Key dates
| Filing date | Apr 11, 1997 |
| Grant date | Aug 15, 2000 |
| Priority date | — |
| Expiry date | Apr 11, 2017 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07K2317/77
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
Mutants of the human PAI-1 protein are described which are inhibitors of neutrophil elastase or are inhibitors of vitronectin (Vn)-dependent cell migration. These mutants preferably comprise one or two amino acid substitutions in the reactive center loop of PAI-1, particularly at positions 331 and 346 of the mature protein. These mutants are notable in being resistant to inactivation by elastase, having high affinity for Vn, or both properties. These mutant proteins as pharmaceutical compositions are used to inhibit elastase in a subject, thereby treating a number of disorders associated with elastase activity, most notably emphysema, ARDS, inflammatory lung injury and cystic fibrosis. The mutants which interact with Vn are used to inhibit cell migration in a subject, thereby treating diseases or conditions associated with undesired cell migration and proliferation, particularly of smooth muscle cells. Such conditions include atherosclerosis, post angioplasty restenosis, fibrosis associated with chronic inflammation or chemotherapy, tumor invasion and metastasis and conditions in which angiogenesis is pathogenic. Also disclosed are peptides of such mutant proteins, mutant-specific …
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.