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1. 发明申请

WO2007106893A2 USE OF THROMBIN MUTANTS TO INHIBIT THE ANTICOAGULATION EFFECT OF THROMBIN INHIBITORS 审中-公开
标题翻译：使用凝血酶抑制剂抑制血红蛋白抑制剂的抗凝作用
公开(公告)号：WO2007106893A2
公开(公告)日：2007-09-20
申请号：PCT/US2007064081
申请日：2007-03-15
申请人： UNIV EMORY , UNIV WASHINGTON , UNIV OREGON HEALTH & SCIENCE , TANAKA KENICHI , DI CERA ENRICO , GRUBER ANDRAS , HANSON STEPHEN RAYMOND
发明人： TANAKA KENICHI , DI CERA ENRICO , GRUBER ANDRAS , HANSON STEPHEN RAYMOND
CPC分类号： A61K38/4833 , G01N33/86 , G01N2333/7452
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.
摘要翻译：本发明提供了抑制凝血酶抑制剂在有需要的患者中的抗凝效果的方法，其包括施用治疗有效量的能够结合凝血酶抑制剂并降低促凝血活性的变体凝血酶原或凝血酶。在本发明的方法中使用的变体前血栓素或血栓素包括其中215位和/或217位的氨基酸为丙氨酸的凝血酶突变体W215A，W215A / E217A或其变体。还提供了其中凝血酶突变体与另外的活性剂，特别是止血剂如活化因子VII或活化的凝血酶原复合物浓缩物一起施用的方法。在本发明的一个实施方案中，所述方法可用于治疗已经施用直接凝血酶抑制剂的患者，特别是阿加曲班。本发明还提供了使用变体凝血酶原或凝血酶滴定测定来定量患者血浆或全血中抗凝血剂浓度的方法。

2. 发明申请

WO02100337A2 ANTITHROMBOTIC THROMBIN VARIANTS 审中-公开
标题翻译：抗生素血红蛋白变异体
公开(公告)号：WO02100337A2
公开(公告)日：2002-12-19
申请号：PCT/US0218211
申请日：2002-06-07
申请人： UNIV EMORY
发明人： GRUBER ANDRAS , HANSON STEPHEN R , DI CERA ENRICO
IPC分类号： A61K38/00 , C12N9/64 , C12N9/74 , C12Q1/40 , G01N33/86 , A61K
CPC分类号： C12N9/6464 , A61K38/00 , C12N9/6429 , C12Q1/40 , C12Y304/21005 , C12Y304/21069 , G01N33/86
摘要： The present invention relates to novel antithrombotic variants of thrombin or fragments thereof that are capable of proteolytically activating protein C, but which are substantially free of fibrinogen cleavage activity. The present invention further relates to variant polypeptides that may be cleaved to yield active thrombin variants. The present invention also relates to methods of inhibiting thrombus formation in an animal or human subject by delivering an antithrombotic variant thrombin of the present invention to the blood of the subject. The present invention relates also to methods that use the novel variant thrombins for determining the level of protein C activation in a blood sample, or the thrombogenic potential of a patient.
摘要翻译：本发明涉及能够蛋白水解活化蛋白C但基本上不含纤维蛋白原裂解活性的凝血酶或其片段的新型抗血栓形成变体。本发明还涉及可被切割以产生活性凝血酶变体的变体多肽。本发明还涉及通过将本发明的抗血栓形成变体凝血酶递送至受试者的血液来抑制动物或人受试者中血栓形成的方法。本发明还涉及使用新型变体血栓素来测定血液样品中蛋白C活化水平或患者血栓形成潜力的方法。

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