USE OF THROMBIN MUTANTS TO INHIBIT THE ANTICOAGULATION EFFECT OF THROMBIN INHIBITORS
    2.
    发明申请
    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

    公开(公告)号:US20130064807A1

    公开(公告)日:2013-03-14

    申请号:US13649281

    申请日:2012-10-11

    IPC分类号: A61K38/48 A61P7/04

    摘要: The present disclosure 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 disclosure 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. In one embodiment, the methods are useful in the treatment of patients in which a direct thrombin inhibitor has been administered. The present disclosure 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: 本公开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,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。 在本公开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位的氨基酸是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一起施用的方法。 在一个实施方案中,所述方法可用于治疗已经施用直接凝血酶抑制剂的患者。 本公开进一步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。

    USE OF THROMBIN MUTANTS TO INHIBIT THE ANTICOAGULATION EFFECT OF THROMBIN INHIBITORS
    4.
    发明申请
    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

    公开(公告)号:US20100158890A1

    公开(公告)日:2010-06-24

    申请号:US12282695

    申请日:2007-03-15

    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.

    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。

    Thrombomodulin-based coagulometric assay of the protein C system
    5.
    发明授权
    Thrombomodulin-based coagulometric assay of the protein C system 失效
    蛋白C系统基于血栓调节蛋白的凝血测定法

    公开(公告)号:US5716795A

    公开(公告)日:1998-02-10

    申请号:US582384

    申请日:1996-01-03

    摘要: The present invention provides a one-stage assay which uses soluble thrombomodulin for directly determining the functional status in plasma of the protein C system. The activity of the protein C system is used to determine the risk of thrombosis in the host individual. Alternatively, the activity of the protein C system is used to determine the presence of a malignant cancer and other pathologies. In another embodiment of the invention, a heparin adsorbent step is added to the assay process which reveals the existence of an additional component in protein C activation, and thus the existence of an additional component in the regulation of blood coagulation.

    摘要翻译: 本发明提供了使用可溶性血栓调节蛋白直接测定蛋白质C系统的血浆中的功能状态的一步法。 蛋白C系统的活性用于确定宿主个体血栓形成的风险。 或者,使用蛋白质C系统的活性来确定恶性癌症和其它病症的存在。 在本发明的另一个实施方案中,将肝素吸附步骤加入到测定过程中,其显示在蛋白C活化中存在另外的组分,并且因此存在另外的组分调节血液凝固。

    Method for estimation of the amount of specific cell types
    7.
    发明授权
    Method for estimation of the amount of specific cell types 有权
    估计特定细胞类型数量的方法

    公开(公告)号:US07405047B2

    公开(公告)日:2008-07-29

    申请号:US10178211

    申请日:2002-06-24

    申请人: Per Venge

    发明人: Per Venge

    IPC分类号: G01N33/53

    摘要: The present invention relates to the estimation of the amount of subtypes of specific cells, for example the number of certain subtypes of leukocytes, by measurements of unique proteins in extracts of blood and other biological material. The knowledge of the number or amount of specific subtypes of white cells is important in the clinical diagnosis and surveillance of subjects with inflammatory disease including infectious disease, cancer, allergy/asthma etc.

    摘要翻译: 本发明涉及通过测量血液和其他生物材料提取物中的独特蛋白质来估计特定细胞亚型的量,例如某些白细胞亚型的数量。 对白细胞特异性亚型数量或数量的了解在包括传染病,癌症,过敏/哮喘等炎症性疾病的受试者的临床诊断和监测中是重要的。

    Soluble thrombomodulin-based one-stage assay for vitamin-K dependent
coagulation-inhibiting proteins
    8.
    发明授权
    Soluble thrombomodulin-based one-stage assay for vitamin-K dependent coagulation-inhibiting proteins 失效
    维生素K依赖性凝血抑制蛋白的可溶性血栓调节蛋白一级检测

    公开(公告)号:US5525478A

    公开(公告)日:1996-06-11

    申请号:US481185

    申请日:1995-06-07

    摘要: The present invention provides a novel one-stage assay which uses soluble thrombomodulin for directly determining the functional status in plasma of the vitamin K-dependent coagulation-inhibiting proteins, protein C and protein S. The method comprises combining a blood plasma test sample and a coagulation-activating substance in a calcium-free solution, then adding soluble thrombomodulin and calcium ions to initiate a coagulation reaction, measuring the time required for the test plasma sample to clot, comparing the measured clot time to that of standard control plasma samples, including protein C- and protein S-deficient plasma controls, and then using the compared clot time values for determining the functional status of protein C and protein S in the individual from whom the test plasma sample was taken. The functional status of the vitamin K-dependent coagulation-inhibiting proteins is used to determine the risk of thrombosis in the host individual.

    摘要翻译: 本发明提供了一种新型的一步法,其使用可溶性血栓调节蛋白直接测定维生素K依赖性凝血抑制蛋白,蛋白C和蛋白S的血浆中的功能状态。该方法包括将血浆测试样品和 然后加入可溶性血栓调节蛋白和钙离子以引发凝血反应,测量血浆样品凝块测试所需的时间,将测得的凝血时间与标准对照血浆样品比较,包括 蛋白质C-和蛋白质S缺乏的血浆对照,然后使用比较的凝块时间值来确定取出测试血浆样品的个体中蛋白质C和蛋白质S的功能状态。 维生素K依赖性凝血抑制蛋白的功能状态用于确定宿主个体血栓形成的风险。