Saint Louis University

Protein C variant

Protein C variant



Alireza R. Rezaie, Likui Yang

Researchers have recently discovered a novel form of activated protein C (APC) which may be a potentially safer drug for treating severe sepsis in patients who experience a higher incidence of bleeding due to the anticoagulant function of APC. This novel form of APC has been genetically engineered (mAPC). Unlike known forms of APC (such as Xigris®), this modified molecule retains the anti-inflammatory activity but none of the anti-coagulant effects. The inventors were also able to show that mAPC retains important physiological characteristics such as lack of apoptosis in vitro and normal binding to endothelia cells.
Recently, recombinant APC (Xigris®) has been withdrawn from the market as a drug for treating severe sepsis patients. There is growing evidence suggesting that the beneficial effect of APC in severe sepsis is separate from its anticoagulant effect and is, at least partially, attributed to its direct protective signaling effect in endothelium. Nevertheless, a major drawback of APC is the increased incidence of bleeding in ~2% of the treated patients. Therefore, there is an urgent need for APC variants with diminished anticoagulant activity while still retaining their cytoprotective effects.
This new invention retains the protective anti-inflammatory and anti-apoptotic properties of wild type APC, but lacks the anticoagulant properties responsible for excessive bleeding in some individuals who receive APC treatment for conditions such as septic shock.

U.S. 7,785,857

Stephanie Kimzey, MBA

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