Eli Lilly and Company

Bruce Edward Gerlitz

Brian W Grinnell

Bryan Edward Jones

David Thompson Berg

Novel protein C derivatives are described. These polypeptides retain the biological activity of the wild-type human protein C with substantially longer half-lives in human blood. These polypeptides will require either less frequent administration and/or smaller dosage than wild-type human protein C in the treatment of vascular occlusive disorders, hypercoagulable states, thrombotic disorders and disease states predisposing to thrombosis.

Protein C derivatives

Novel human protein C derivatives are described. These derivatives have increased anti-coagulation activity and resistance to inactivation by serpins, compared to wild-type protein C and retain the biological activity of the wild-type human protein D. These derivatives will require either less frequent administration and/or smaller dosage than wild-type human protein C in the treatment of acute coronary syndromes, vascular occlusive disorders, hyper coagulable states, thrombotic disorders and disease states predisposing to thrombosis.

Novel human protein C derivatives are described. These derivatives have increased anti-coagulation activity, resistance to serpin inactivation, and increased sensitivity to thrombin activation compared to wild-type protein C and retain the biological activity of the wild-type human protein C. These derivatives will require either less frequent administration and/or smaller dosage than wild-type human protein C in the treatment of acute coronary syndromes, vascular occlusive disorders, hypercoagulable states, thrombotic disorders and disease states predisposing to thrombosis.

A method for the recombinant production of forms of human protein C with higher activity is described. These forms differ from native protein C in their increased amidolytic and functional activities and novel carbohydrate structures. DNA compounds, vectors, and transformants useful in the method are also disclosed.

Vectors and compounds for expression of glycosylation mutants of human

Human protein C derivatives with high activity and reduced dependence on thrombin activation are described. These derivatives differ from the native forms of human protein C in their increased activation rates, functional activities and carbohydrate structures. DNA compounds, transfer vectors, expression vectors and transformants useful in producing these derivatives are also described.

A method for the recombinant production of zymogen forms of human protein C is described. These zymogen forms differ from native zymogen protein C in their increased sensitivity to activation by thrombin and thrombin/thrombomodulin. DNA compounds, vectors, and transformants useful in the method are also disclosed.

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Indianapolis, IN, United States of America

Bruce Edward Gerlitz