The goal of the proposed work is to develop a novel antithrombotic drug that is safer and more effective than current therapies. Phase I funding for this project supported the successful development of a novel expression system to facilitate efficient production and purification of an optimized human apyrase as antithrombotic agent. Under Phase II support, we will extend the feasibility studies of Phase I to the development of a commercial Chinese hamster ovary cell line for high yield production. We will then utilize the recombinant protein to determine whether inhibition of platelet activation with the optimized apyrase in vivo attenuates thrombosis after arterial injury in rabbits and pigs. The ultimate goal of this research will be to develop APT102 as a frontline therapy for patients undergoing percutaneous coronary intervention as well as other patients with vascular disorders induced by excessive platelet activation. ? ?