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公开(公告)号：US08450275B2
公开(公告)日：2013-05-28
申请号：US13026070
申请日：2011-02-11
申请人： Michael Dockal , Rudolf Hartmann , Markus Fries , Friedrich Scheiflinger , Hartmut Ehrlich , Ulrich Reineke , Frank Osterkamp , Thomas Polakowski
发明人： Michael Dockal , Rudolf Hartmann , Markus Fries , Friedrich Scheiflinger , Hartmut Ehrlich , Ulrich Reineke , Frank Osterkamp , Thomas Polakowski
IPC分类号： A61K38/57
CPC分类号： A61K38/10 , A61K38/00 , A61K2121/00 , C07K1/14 , C07K7/08 , C07K14/00 , C07K14/8114 , G01N33/68 , G01N2333/745 , G01N2333/8114 , G01N2333/96444 , G01N2333/96447 , G01N2500/02 , G01N2500/04 , G01N2500/20 , G06F19/16 , G06F19/18
摘要： The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, treat a blood coagulation disorder in a subject, purify TFPI, and identify a TFPI-binding compound.
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公开(公告)号：US08466108B2
公开(公告)日：2013-06-18
申请号：US12643818
申请日：2009-12-21
申请人： Michael Dockal , Hartmut Ehrlich , Friedrich Scheiflinger , Ulf Reimer , Ulrich Reineke , Thomas Polakowski , Eberhard Schneider
发明人： Michael Dockal , Hartmut Ehrlich , Friedrich Scheiflinger , Ulf Reimer , Ulrich Reineke , Thomas Polakowski , Eberhard Schneider
IPC分类号： A61K38/36 , A61K38/37 , A61K38/10 , A61K38/00 , A61K38/04 , A61K38/16 , C07K14/745 , C07K14/755
CPC分类号： C07K14/4703 , A61K38/00 , A61K47/551 , A61K47/557 , A61K47/60 , C07K7/08 , C07K14/001 , Y02A50/463
摘要： The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, and/or treat a blood coagulation disorder in a subject.
摘要翻译： 本发明提供了结合组织因子途径抑制剂（TFPI），包括TFPI抑制肽的肽及其组合物。 肽可以用于抑制TFPI，增强凝血因子缺陷受试者中的凝血酶形成，增加受试者中的血块形成和/或治疗受试者的血液凝固障碍。
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公开(公告)号：US20100173847A1
公开(公告)日：2010-07-08
申请号：US12643818
申请日：2009-12-21
申请人： Michael Dockal , Hartmut Ehrlich , Friedrich Scheiflinger , Ulf Reimer , Ulrich Reineke , Thomas Polakowski , Eberhard Schneider
发明人： Michael Dockal , Hartmut Ehrlich , Friedrich Scheiflinger , Ulf Reimer , Ulrich Reineke , Thomas Polakowski , Eberhard Schneider
CPC分类号： C07K14/4703 , A61K38/00 , A61K47/551 , A61K47/557 , A61K47/60 , C07K7/08 , C07K14/001 , Y02A50/463
摘要： The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, and/or treat a blood coagulation disorder in a subject.
摘要翻译： 本发明提供了结合组织因子途径抑制剂（TFPI），包括TFPI抑制肽的肽及其组合物。 肽可以用于抑制TFPI，增强凝血因子缺陷受试者中的凝血酶形成，增加受试者中的血块形成和/或治疗受试者的血液凝固障碍。
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公开(公告)号：US08632991B2
公开(公告)日：2014-01-21
申请号：US13006396
申请日：2011-01-13
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：US08435792B2
公开(公告)日：2013-05-07
申请号：US13111684
申请日：2011-05-19
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.
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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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公开(公告)号：US20080214461A1
公开(公告)日：2008-09-04
申请号：US12022059
申请日：2008-01-29
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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9.发明授权公开(公告)号：US08022187B2
公开(公告)日：2011-09-20
申请号：US12022059
申请日：2008-01-29
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：US20080214462A1
公开(公告)日：2008-09-04
申请号：US12022071
申请日：2008-01-29
CPC分类号： C12N9/644 , C12Y304/21022
摘要： The present invention relates to recombinant blood coagulation factor IX (rFIX) mutants having improved FIX clotting activity. Three 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) assays in FIX-depleted plasma. Two mutant proteins had increased specific FIX activity. Furthermore, a pre-activated FIX protein had an increased activity in FIX-depleted plasma. Therefore these FIX mutants can be used for the treatment of FIX associated bleeding disorders.
摘要翻译： 本发明涉及具有改善的FIX凝血活性的重组凝血因子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三个全长FIX蛋白。 通过在FIX消耗的血浆中的活化部分凝血活酶时间（aPTT）测定来测试蛋白质。 两种突变蛋白具有增加的特异性FIX活性。 此外，预活化的FIX蛋白在FIX耗尽的血浆中具有增加的活性。 因此，这些FIX突变体可用于治疗FIX相关出血性疾病。
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