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公开(公告)号：US08822638B2
公开(公告)日：2014-09-02
申请号：US13238751
申请日：2011-09-21
IPC分类号： C07K7/00
摘要： A peptide or peptide derivative comprising: (i) WDLYFEIVW;(SEQ ID NO: 1) or (ii) a variant amino acid sequence comprising one, two, three or four L-amino acid substitutions in WDLYFEIVW (SEQ ID NO: 1); or (iii) the retro-inverso variant of the peptide or peptide derivative of either one of parts (i) and (ii), wherein said peptide or peptide derivative has procoagulant activity. A peptide or peptide derivative comprising: (i) an amino acid sequence comprising imfwydcye; or (ii) a variant amino acid sequence comprising one, two, three, four, five or six amino acid substitutions in imfwydcye, wherein said peptide or peptide derivative has procoagulant activity.
摘要翻译： 一种肽或肽衍生物，其包含：（i）WDLYFEIVW; （SEQ ID NO：1）或（ii）在WDLYFEIVW（SEQ ID NO：1）中包含一个，两个，三个或四个L-氨基酸取代的变体氨基酸序列; 或（iii）部分（i）和（ii）中任一项的肽或肽衍生物的逆转型变体，其中所述肽或肽衍生物具有促凝活性。 一种肽或肽衍生物，其包含：（i）包含成纤维细胞的氨基酸序列; 或（ii）在成纤维细胞中包含一个，两个，三个，四个，五个或六个氨基酸取代的变体氨基酸序列，其中所述肽或肽衍生物具有促凝活性。
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32.发明授权Immunoadsorption of anti-von Willebrand factor cleaving protease antibodies 有权抗von Willebrand因子切割蛋白酶抗体的免疫吸附公开(公告)号：US08795999B2
公开(公告)日：2014-08-05
申请号：US12388450
申请日：2009-02-18
CPC分类号： C12N9/6416 , A61K2039/505 , C07K14/755 , C07K16/40 , C12Q1/56 , G01N33/86
摘要： This invention relates to adsorbents and methods for highly selective removal of anti-von Willebrand Factor-cleaving protease antibodies (“anti-vWF-cp-abs”) from human plasma using human von Willebrand Factor-cleaving protease (“hvWF-cp”) or fragments thereof as affinity ligands. The adsorbents can be used for treating disorders associated with the occurrence of anti-vWF-cp-abs in patients, such as thromboembolic diseases.
摘要翻译： 本发明涉及使用人血管性血友病因子切割蛋白酶（“hvWF-cp”）从人血浆中高度选择性除去抗血管性血友病因子切割蛋白酶抗体（“anti-vWF-cp-abs”）的吸附剂和方法。 或其片段作为亲和配体。 吸附剂可用于治疗与患者中抗vWF-cp-abs的发生相关的疾病，例如血栓栓塞性疾病。
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公开(公告)号：US08563688B2
公开(公告)日：2013-10-22
申请号：US12425277
申请日：2009-04-16
摘要： A peptide or peptide derivative comprising: (i) WDLYFEIVW (SEQ ID NO: 1); or (ii) a variant amino acid sequence comprising one, two, three or four L-amino acid substitutions in WDLYFEIVW (SEQ ID NO: 1); or (iii) the retro-inverso variant of the peptide or peptide derivative of either one of parts (i) and (ii), wherein said peptide or peptide derivative has procoagulant activity. A peptide or peptide derivative comprising: (i) an amino acid sequence comprising imfwydcye; or (ii) a variant amino acid sequence comprising one, two, three, four, five or six amino acid substitutions in imfwydcye, wherein said peptide or peptide derivative has procoagulant activity.
摘要翻译： 一种肽或肽衍生物，其包含：（i）WDLYFEIVW（SEQ ID NO：1）; 或（ii）在WDLYFEIVW（SEQ ID NO：1）中包含一个，两个，三个或四个L-氨基酸取代的变体氨基酸序列; 或（iii）部分（i）和（ii）中任一项的肽或肽衍生物的逆转型变体，其中所述肽或肽衍生物具有促凝活性。 一种肽或肽衍生物，其包含：（i）包含成纤维细胞的氨基酸序列; 或（ii）在成纤维细胞中包含一个，两个，三个，四个，五个或六个氨基酸取代的变体氨基酸序列，其中所述肽或肽衍生物具有促凝活性。
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公开(公告)号：US08546332B2
公开(公告)日：2013-10-01
申请号：US12388665
申请日：2009-02-19
申请人： Petrus Johannes Lenting , Jan Aart Van Mourik , Koenraad Mertens , Hans Pannekoek , Peter Turecek , Hans-Peter Schwarz , Friedrich Scheiflinger
发明人： Petrus Johannes Lenting , Jan Aart Van Mourik , Koenraad Mertens , Hans Pannekoek , Peter Turecek , Hans-Peter Schwarz , Friedrich Scheiflinger
CPC分类号： C07K14/755 , A61K38/00 , A61K38/37 , C07K14/705 , A61K2300/00
摘要： Factor VIII polypeptides having FVIII:C activity that contain modifications in the A3 and/or C1 and/or C2 domains of the sequence of the light chain of Factor VIII, characterized by the binding affinity to low density lipoprotein receptor protein, and methods for producing the same.
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35.发明授权Method for identifying a non-anticoagulant sulfated polysaccharide which enhances blood coagulation dependence on FXI 有权鉴定增强血液凝固依赖于FXI的非抗凝血硫酸多糖的方法公开(公告)号：US08546096B2
公开(公告)日：2013-10-01
申请号：US13002501
申请日：2009-08-21
IPC分类号： C12Q1/56
CPC分类号： A61K31/737 , A61K31/727 , A61K38/36 , A61K38/366 , A61K38/37 , A61K38/4846 , A61K38/4853 , A61K45/06 , G01N33/86 , A61K2300/00
摘要： A method of identifying a non-anticoagulant sulfated polysaccharide (NASP) which is capable of enhancing blood coagulation in dependence of FXI, the method comprising: a) combining a blood or plasma sample having activation competent FXI with a sulfated polysaccharide and measuring the clotting or thrombin generation parameters of the blood or plasma sample; b) combining a corresponding blood or plasma sample deficient In activation competent FXI with a sulfated polysaccharide and measuring the clotting or thrombin generation parameters of the blood or plasma sample and c) comparing the clotting or thrombin generation parameters of the blood or plasma samples as determined in steps (a) and (b) with each other.
摘要翻译： 一种鉴定能够根据FXI增强血液凝固的非抗凝血硫酸多糖（NASP）的方法，所述方法包括：a）将具有活化能力的FXI的血液或血浆样品与硫酸化多糖组合并测量凝血或 血液或血浆样品的凝血酶产生参数; b）将活化能力FXI中缺乏的相应血液或血浆样品与硫酸化多糖组合并测量血液或血浆样品的凝血酶或凝血酶产生参数; c）比较测定的血液或血浆样品的凝血酶或凝血酶产生参数 在步骤（a）和（b）中。
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公开(公告)号：US08513386B2
公开(公告)日：2013-08-20
申请号：US13096894
申请日：2011-04-28
IPC分类号： A61K35/14 , A61K38/36 , C07K14/745
CPC分类号： C12N9/644 , A61K38/00 , C12Y304/21022
摘要： The present invention relates to recombinant blood coagulation factor IX (rFIX) mutants having factor VIII (FVIII) independent factor X (FX) activation potential. Five full length FIX proteins with combinations of mutations of amino acids important for functional activity of FIX and FIX wild type were cloned and expressed in HEK 293 cells. The proteins were tested by an activated partial thromboplastin time (aPTT) assay in FVIII-depleted plasma as well as in FVIII-inhibited patient plasma. In FVIII-depleted plasma functional activity of the FIX mutants was calculated as increased FVIII equivalent activity. The mutant proteins had increased FVIII equivalent activity. In FVIII-inhibited patient plasma the FEIBA equivalent activity was calculated for analysis of FVIII independent FX activation potential. The proteins had also increased FEIBA equivalent activity. Furthermore, the pre-activated FIX proteins had an increased activity in FIX-depleted plasma containing FVIII inhibitors. Therefore these FIX mutants are alternatives as bypassing agents for treatment of FVIII inhibitor patients.
摘要翻译： 本发明涉及具有因子VIII（FVIII）独立因子X（FX）活化电位的重组凝血因子IX（rFIX）突变体。 在HEK 293细胞中克隆并表达具有FIX和FIX野生型功能活性重要的氨基酸突变组合的五个全长FIX蛋白。 通过在FVIII消除的血浆以及FVIII抑制的患者血浆中的活化部分凝血活酶时间（aPTT）测定来测试蛋白质。 在FVIII消耗的血浆中，FIX突变体的功能活性被计算为增加的FVIII当量活性。 突变蛋白具有增加的FVIII当量活性。 在FVIII抑制的患者血浆中，计算FEIBA等效活性以分析FVIII独立的FX激活电位。 蛋白质也增加了FEIBA等效活性。 此外，预活化的FIX蛋白在含有FVIII抑制剂的FIX耗尽血浆中具有增加的活性。 因此，这些FIX突变体是用于治疗FVIII抑制剂患者的旁路药物的替代物。
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公开(公告)号：US08076463B2
公开(公告)日：2011-12-13
申请号：US13007208
申请日：2011-01-14
CPC分类号： C07K14/755 , A61K47/60 , C07K14/775
摘要： The present invention relates to a proteinaceous construct (also designated as polymer-VWF-conjugate) comprising plasmatic and/or recombinant von Willebrand factor (VWF), said VWF being bound to at least one physiologically acceptable polymer molecule, as well as to a complex between said proteinaceous construct and at least one factor VIII (FVIII) protein. The physiologically acceptable polymer molecule can be, for instance, polyethylene glycol (PEG) or polysialic acid (PSA). Further the present invention relates to methods for prolonging the in vivo-half-life of VWF or FVIII in the blood of a mammal having a bleeding disorder associated with functional defects of or deficiencies of at least one of FVIII or VWF.
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公开(公告)号：US20110244478A1
公开(公告)日：2011-10-06
申请号：US13111684
申请日：2011-05-19
IPC分类号： G01N33/566 , C08B37/00 , C12Q1/56 , C12P19/04
CPC分类号： G01N33/86 , A61K31/737 , A61K38/36 , A61K38/37 , Y10T436/106664 , Y10T436/107497 , Y10T436/178459 , Y10T436/18 , Y10T436/255 , A61K2300/00
摘要： Aspects of the invention include methods for enhancing blood coagulation in a subject. In practicing methods according to certain embodiments, an amount of a non-anticoagulant sulfated polysaccharide (NASP) is administered to a subject to enhance blood coagulation in the subject. Also provided are methods for preparing a NASP composition having blood coagulation enhancing activity. Compositions and kits for practicing methods of the invention are also described.
摘要翻译： 本发明的方面包括用于增强受试者血液凝固的方法。 在根据某些实施方案的实践方法中，将一定量的非抗凝血硫酸多糖（NASP）施用于受试者以增强受试者的血液凝固。 还提供了制备具有凝血增强活性的NASP组合物的方法。 还描述了用于本发明的实践方法的组合物和试剂盒。
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公开(公告)号：US20110172156A1
公开(公告)日：2011-07-14
申请号：US13006396
申请日：2011-01-13
IPC分类号： A61K38/36 , A61K31/737 , A61K38/37 , C07H5/10 , A61P7/02
CPC分类号： G01N33/86 , A61K31/737 , A61K38/36 , A61K38/37 , Y10T436/106664 , Y10T436/107497 , Y10T436/178459 , Y10T436/18 , Y10T436/255 , A61K2300/00
摘要： Aspects of the invention include methods for enhancing blood coagulation in a subject. In practicing methods according to certain embodiments, an amount of a non-anticoagulant sulfated polysaccharide (NASP) is administered to a subject to enhance blood coagulation in the subject. Also provided are methods for preparing a NASP composition having blood coagulation enhancing activity. Compositions and kits for practicing methods of the invention are also described.
摘要翻译： 本发明的方面包括用于增强受试者血液凝固的方法。 在根据某些实施方案的实践方法中，将一定量的非抗凝血硫酸多糖（NASP）施用于受试者以增强受试者的血液凝固。 还提供了制备具有凝血增强活性的NASP组合物的方法。 还描述了用于本发明的实践方法的组合物和试剂盒。
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40.发明申请DIAGNOSTIC ASSAY FOR ANTI-VON WILLEBRAND FACTOR CLEAVING PROTEASE (ADAMTS13) ANTIBODIES 有权用于抗血栓威因因子（ADAMTS13）抗体的诊断测定公开(公告)号：US20100273183A1
公开(公告)日：2010-10-28
申请号：US12829872
申请日：2010-07-02
IPC分类号： G01N33/53
摘要： This invention relates to a kit to be used in an assay system for determination of an anti-von Willebrand Factor-cleaving protease (“anti-vWF-cp”) antibody in a sample. The kit comprises vWF-cp and/or vWF-fragment(s) immobilized on a solid phase. The kit can be used in a method for determination of anti-vWF-cp antibodies from a patient, for the diagnosis of disorders associated with the occurrence of anti-vWF-cp-antibodies, and the differentiation of various forms of thrombotic microangiopathy.
摘要翻译： 本发明涉及一种用于测定样品中抗血管性血友病因子切割蛋白酶（“vWF-cp”）抗体的测定系统的试剂盒。 该试剂盒包含固定在固相上的vWF-cp和/或vWF-片段。 该试剂盒可用于测定来自患者的抗vWF-cp抗体的方法，用于诊断与抗vWF-cp抗体发生相关的病症，以及各种形式的血栓性微血管病变的分化。
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