Thrombomodulin analogs for pharmaceutical use
AssigneeSchering Corporation
InventorsDavid Light, Michael John Morser, Mariko Nagashima
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Abstract
The present invention relates to the design, production and use of analogs of thrombomodulin (TM) that have the ability to enhance the thrombin-mediated activation of protein C but which have a significantly reduced ability to promote activation of thrombin-activatable fibrinolysis inhibitor (TAFI). These analogs are useful in, for example, antithrombotic therapy.
Claims16
A thrombomodulin analog, wherein the amino acid sequence of native thrombomodulin (SEQ ID NO:
- 2) is modified at positions 340, 341, or 343 and at position 381, and wherein the modified analog has greater than 100% of the ability to potentiate thrombin-mediated activation of protein C and less than 50% of the ability to potentiate thrombin-mediated activation of TAFI, as compared with native thrombomodulin (SEQ ID NO:
- 2).
A sterile composition useful for treating a thrombotic disease or condition in mammals, comprising a therapeutically effective dose of a purified thrombomodulin analog, wherein the amino acid sequence of native thrombomodulin (SEQ ID NO:
- 2) is modified at positions 340, 341, or 343 and at position 381, and wherein the modified analog has greater than 100% of the ability to potentiate thrombin-mediated activation of protein C and less than 50% of the ability to potentiate thrombin-mediated activation of TAFI, as compared with native thrombomodulin (SEQ ID NO:
- 2).
Dependencies are inferred from the claim text.