Mutant APC molecules improve survival in sepsis

 Mutant APC molecules that lack anticoagulant activity and the associated bleedingcomplications are expected to improve patient survival Bolus dosing of the drug offers more simplified use Exclusively licensed in 2010

Numerous in vivo studies document the beneficial effects of APC. Recombinant activated protein C (rAPC), sold as Xigris® (Eli Lilly), is approved for treating severe sepsis. However, clinical studies have shown APC treatment to be associated with increased risk of serious bleeding. This increased risk of bleeding presents a major limitation of current APC therapy. Mutants of APC retaining the beneficial anti-inflammatory and cytoprotective effects but with low anticoagulant activity hold promise as an improved form of APC therapy. Moreover, there is evidence that the full anticoagulant activity of APC might impair mechanisms involving the beneficial fibrin-dependent clearance of bacteria. An additional benefit discovered is simplifieddosing. Current treatment methods employing APC involve continuous infusions. It is an object of this invention to improve and simplify the use of APC or APC variants for treatment of sepsis.US and PCT filed October 31, 2007 with priority to October 31, 2006. Publication number WO/08/073603Work was described in the #1 abstract and plenary session for the 2007 Am Society of Hemotology.

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