| abstract |
It provides a variant of recombinant active protein C (APC) or recombinant protein C (prodrug that can be converted to APC) which substantially reduces anticoagulant activity but maintains anti-apoptotic activity. Two examples of such recombinant APC variants are 3K3A-APC and 229 / 230-APC. The APC variants and prodrugs of the present invention possess desirable properties of cytoprotective effects (anti-apoptotic effects) and a significant reduction in the risk of bleeding. The present invention also provides a method of using the APC variant or prodrug to treat a patient who would benefit from the cytoprotective activity of APC regardless of the anticoagulant activity of APC. These subjects include patients at least partially exposed to risk of damage to blood vessels or tissues of various organs due to cell death. Patients at risk include, among other conditions, for example, sepsis, ischemia / reperfusion injury, ischemic stroke, acute myocardial infarction, acute or chronic neurodegenerative disease, or organ transplantation or chemotherapy. Methods of screening variants of useful recombinant protein C or APC according to the invention are also provided. |