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1. 发明申请

WO2009067660A3 ANTI-FACTOR XI MONOCLONAL ANTIBODIES AND METHODS OF USE THEREOF 审中-公开
标题翻译：抗因子XI单克隆抗体及其使用方法
公开(公告)号：WO2009067660A3
公开(公告)日：2009-07-09
申请号：PCT/US2008084336
申请日：2008-11-21
申请人： UNIV OREGON HEALTH & SCIENCE , UNIV VANDERBILT , GRUBER ANDRAS , TUCKER ERIK IAN , HANSON STEPHEN RAYMOND , GAILANI DAVID
发明人： GRUBER ANDRAS , TUCKER ERIK IAN , HANSON STEPHEN RAYMOND , GAILANI DAVID
IPC分类号： C07K16/36
CPC分类号： C07K16/36 , A61K39/3955 , A61K45/06 , A61K2039/505 , C07K2316/96 , C07K2317/24 , C07K2317/32 , C07K2317/54 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/624 , C07K2317/76 , C07K2317/92
摘要： The present invention relates to compositions and methods for inhibiting thrombosis without compromising hemostasis. Compositions include anti-factor XI monoclonal antibodies (aXIMabs) capable of binding to an epitope on the heavy chain of human FXI, particularly the A3 domain of the heavy chain of human FXI. Compositions also include epitope-binding fragments, variants, and derivatives of the monoclonal antibodies, cell lines producing these antibody compositions, and isolated nucleic acid molecules encoding the amino acid sequences of the antibodies. The invention further includes pharmaceutical compositions comprising the anti-factor XI monoclonal antibodies of the invention, or epitope-binding fragments, variants, or derivatives thereof, in a pharmaceutically acceptable carrier. Methods of the invention comprise administering the compositions described above to a subject in need thereof for the purpose of inhibiting thrombosis, reducing a required dose of an antithrombotic agent in the treatment of thrombosis, treating metastatic cancer, or treating an acute inflammatory reaction. Methods for making an anti-factor XI monoclonal antibody, or epitope-binding fragments, variants, or derivatives thereof, are also provided.
摘要翻译：本发明涉及用于抑制血栓形成而不损害止血的组合物和方法。组合物包括能够结合人FXI的重链上的表位，特别是人FXI重链的A3结构域的抗因子XI单克隆抗体（aXIMabs）。组合物还包括单克隆抗体的表位结合片段，变体和衍生物，产生这些抗体组合物的细胞系和编码抗体的氨基酸序列的分离的核酸分子。本发明进一步包括在药学上可接受的载体中包含本发明的抗因子XI单克隆抗体或其表位结合片段，变体或衍生物的药物组合物。本发明的方法包括向有需要的受试者施用上述组合物，用于抑制血栓形成，在治疗血栓形成中减少抗血栓形成剂的剂量，治疗转移性癌症或治疗急性炎症反应。还提供了制备抗因子XI单克隆抗体或其表位结合片段，变体或衍生物的方法。

2. 发明申请

WO2010080623A3 ANTI-FXI ANTIBODIES AND METHODS OF USE 审中-公开
标题翻译：抗FXI抗体和使用方法
公开(公告)号：WO2010080623A3
公开(公告)日：2010-11-18
申请号：PCT/US2009068768
申请日：2009-12-18
申请人： UNIV OREGON HEALTH & SCIENCE , UNIV VANDERBILT , GRUBER ANDRAS , TUCKER ERIK I , GAILANI DAVID
发明人： GRUBER ANDRAS , TUCKER ERIK I , GAILANI DAVID
IPC分类号： C07K16/36 , A61K39/395 , A61P7/02 , C12N15/13
CPC分类号： C07K16/36 , A61K2039/505 , C07K2316/96 , C07K2317/24 , C07K2317/569 , C07K2317/73 , C07K2317/76
摘要： Disclosed herein are monoclonal antibodies specific for factor XI (fXI) that prevent activation of fXI by factor XIIa (fXIIa). The monoclonal antibodies are universal fXI antibodies, capable of binding all mammalian species tested. The anti- fXI monoclonal antibodies prolong clotting time in mammalian plasmas. Moreover, administration of the fXI monoclonal antibodies disclosed herein results in inhibition of thrombosis without altering hemostasis in animal models of thrombosis. Thus, provided herein are monoclonal antibodies specific for fXI that block activation of fXI by fXIIa, compositions and immunoconjugates comprising such antibodies and their methods of use.
摘要翻译：本文公开了阻止因子XIIa（fXIIa）激活fXI的因子XI（fXI）特异性单克隆抗体。单克隆抗体是通用fXI抗体，能够结合所有测试的哺乳动物物种。抗fXI单克隆抗体可延长哺乳动物血浆中的凝血时间。此外，本文公开的fXI单克隆抗体的施用导致血栓形成的抑制而不改变血栓形成的动物模型中的止血。因此，本文提供了阻断fXIIa激活fXI的fXI特异性单克隆抗体，包含此类抗体的组合物和免疫偶联物及其使用方法。

3. 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。

4. 发明申请

WO2008157593A3 PROTEIN C FOR USE IN MAINTAINING HEMOSTASIS 审中-公开
标题翻译：蛋白C用于维持HEMOSTASIS
公开(公告)号：WO2008157593A3
公开(公告)日：2009-03-19
申请号：PCT/US2008067321
申请日：2008-06-18
申请人： UNIV OREGON HEALTH & SCIENCE , SCRIPPS RESEARCH INST , MCCARTY OWEN J T , GRUBER ANDRAS , GRIFFIN JOHN H
发明人： MCCARTY OWEN J T , GRUBER ANDRAS , GRIFFIN JOHN H
IPC分类号： A61K38/48 , A61P7/02 , A61P7/04
CPC分类号： A61K38/4866
摘要： It is disclosed herein that protein C functions as a hemostatic agent. Thus, provided is a method of preventing, treating or ameliorating abnormal bleeding in a subject, comprising administering to the subject a protein C polypeptide or polynucleotide. Abnormal bleeding can result from a bleeding disorder, such as hemophilia or a platelet disorder, or from a bleeding episode, such as from a traumatic injury.
摘要翻译：本文公开了蛋白C作为止血剂。因此，提供了预防，治疗或改善受试者异常出血的方法，其包括对受试者施用蛋白C多肽或多核苷酸。异常出血可能是出血性疾病，如血友病或血小板疾病，或出血发作，如创伤性损伤。

5. 发明申请

WO2012088220A3 EXPRESSION OF THROMBIN VARIANTS 审中-公开
标题翻译：表达THROMBIN变体
公开(公告)号：WO2012088220A3
公开(公告)日：2014-04-10
申请号：PCT/US2011066377
申请日：2011-12-21
申请人： UNIV SAINT LOUIS , DI CERA ENRICO , GRUBER ANDRAS , GANDHI PRAFULL , PELC LESLIE , POZZI NICOLA , WOOD DAVID COLLIER
发明人： DI CERA ENRICO , GRUBER ANDRAS , GANDHI PRAFULL , PELC LESLIE , POZZI NICOLA , WOOD DAVID COLLIER
IPC分类号： A61K38/48 , A61P7/02 , C12N9/74
CPC分类号： C12N9/6429 , A61K38/4833 , C12Y304/21005
摘要： One aspect of the invention contemplates a mutant E-WE thrombin precursor that contains the SEQ ID NO:1 amino acid residue sequence. Another aspect contemplates a thrombin precursor that contains the amino acid residue sequence Asp/Glu-Gly-Arg at positions 325, 326 and 327 based on the preprothrombin sequence. A third aspect contemplates a thrombin precursor that contains the SEQ ID NO:1 amino acid residue sequence as well as the amino acid residue sequence Asp/Glu Gly Arg at positions 325, 326 and 327 based on the preprothrombin sequence. Also contemplated is a composition that contains an effective amount of mutant thrombin dissolved or dispersed in a pharmaceutically acceptable carrier. A method is also disclosed for enhancing treating and preventing thrombosis in a mammal in need using that composition.
摘要翻译：本发明的一个方面考虑了含有SEQ ID NO：1氨基酸残基序列的突变E-WE凝血酶前体。另一方面考虑了基于前凝血酶原序列在325,326和327位含有氨基酸残基序列Asp / Glu-Gly-Arg的凝血酶前体。第三方面考虑了基于前凝血酶原序列的含有SEQ ID NO：1氨基酸残基序列以及位置325,326和327的氨基酸残基序列Asp / Glu Gly Arg的凝血酶前体。还考虑了包含溶解或分散在药学上可接受的载体中的有效量的突变凝血酶的组合物。还公开了一种用于增强使用该组合物治疗和预防需要的哺乳动物血栓形成的方法。

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