Griffin, John H.,Gale, Andrew J.,Mosnier, Laurent O.
申请号：
AU2007313715
公开号：
AU2007313715B2
申请日:
2007.10.30
申请国别(地区):
AU
年份:
2013
代理人:
摘要：
Variants (mutants) of recombinant activated protein C (APC) or recombinantprotein C (prodrug, capable of being converted to APC) that have substantialreductions in anticoagulant activity but that retain normal levels of anti-apoptoticactivity are provided. Three examples of such recombinant APC mutants are KKK191-193AAA-APC,RR229/230AA-APC, and RR229/230AA plus KKK191-193AAA-APC. APC variants andprodrugs of the invention have the desirable property of being cytoprotective(anti-apoptotic effects), while having significantly reduced risk of bleeding.The invention also provides a method of using the APC variants or prodrugs of theinvention to treat subjects who will benefit from APC's cytoprotectiveactivities that are independent of APC's anticoagulant activity. Thesesubjects include patients at risk of damage to blood vessels or tissue in variousorgans caused, at least in part, by apoptosis. At risk patients include, for example,those suffering (severe) sepsis, ischemia/reperfusion injury, ischemic stroke,acute myocardial infarction, acute or chronic neurodegenerative diseases,or those undergoing organ transplantation or chemotherapy, among other conditions.Methods of screening for variants of recombinant protein C or APC that are usefulin accordance with the invention are also provided.
