发明申请
US20100158890A1 USE OF THROMBIN MUTANTS TO INHIBIT THE ANTICOAGULATION EFFECT OF THROMBIN INHIBITORS
审中-公开
使用凝血酶抑制剂抑制血红蛋白抑制剂的抗凝作用
- 专利标题: USE OF THROMBIN MUTANTS TO INHIBIT THE ANTICOAGULATION EFFECT OF THROMBIN INHIBITORS
- 专利标题(中): 使用凝血酶抑制剂抑制血红蛋白抑制剂的抗凝作用
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申请号: US12282695申请日: 2007-03-15
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公开(公告)号: US20100158890A1公开(公告)日: 2010-06-24
- 发明人: Kenichi Tanaka , Enrico Di Cera , Andras Gruber , Stephen Raymond Hanson
- 申请人: Kenichi Tanaka , Enrico Di Cera , Andras Gruber , Stephen Raymond Hanson
- 国际申请: PCT/US07/64081 WO 20070315
- 主分类号: A61K38/48
- IPC分类号: A61K38/48 ; G01N33/53 ; A61P7/04
摘要:
The present invention provides methods for inhibiting the anticoagulation effect of a thrombin inhibitor in a patient in need thereof comprising administration of a therapeutically effective amount of a variant prothrombin or thrombin that is capable of binding the thrombin inhibitor and that has reduced procoagulant activity. Variant prothrombins or thrombins of use in the methods of the present invention include thrombin mutants W215A, W215A/E217A, or variants thereof in which the amino acids at positions 215 and/or 217 are alanine. Methods are also provided in which the thrombin mutants are administered with an additional active agent, particularly hemostatic agents such as activated factor VII or activated prothrombin complex concentrate. In one embodiment of the invention, the methods are useful in the treatment of patients in which a direct thrombin inhibitor has been administered, particularly argatroban. The present invention further provides a method for quantifying the concentration of an anticoagulant in the plasma or whole blood of a patient using a variant prothrombin or thrombin titration assay.