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1. 发明申请

WO2011115712A8 TFPI INHIBITORS AND METHODS OF USE 审中-公开
标题翻译： TFPI抑制剂及其使用方法
公开(公告)号：WO2011115712A8
公开(公告)日：2013-10-10
申请号：PCT/US2011024604
申请日：2011-02-11
申请人： BAXTER INT , BAXTER HEALTHCARE SA , DOCKAL MICHAEL , HARTMANN RUDOLF , FRIES MARKUS , SCHEIFLINGER FRIEDRICH , EHRLICH HARTMUT , REINEKE ULRICH , OSTERKAMP FRANK , POLAKOWSKI THOMAS
发明人： DOCKAL MICHAEL , HARTMANN RUDOLF , FRIES MARKUS , SCHEIFLINGER FRIEDRICH , EHRLICH HARTMUT , REINEKE ULRICH , OSTERKAMP FRANK , POLAKOWSKI THOMAS
IPC分类号： A61K38/18 , A61K38/16 , C40B40/10
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.
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）及其组合物的肽。肽可以用于抑制TFPI，增强凝血因子缺陷的受试者中的凝血酶形成，增加受试者的血块形成，治疗受试者的血液凝固障碍，纯化TFPI和鉴定TFPI结合化合物。

2. 发明申请

WO2008092644A3 FVIII-INDEPENDENT FIX-MUTANT PROTEINS FOR HEMOPHILIA A TREATMENT 审中-公开
标题翻译：用于HEMOPHILIA治疗的FVIII独立固定蛋白
公开(公告)号：WO2008092644A3
公开(公告)日：2008-10-09
申请号：PCT/EP2008000685
申请日：2008-01-29
申请人： BAXTER INT , BAXTER HEALTHCARE SA , DOCKAL MICHAEL , HARTMANN RUDOLF , SCHEIFLINGER FRIEDRICH
发明人： DOCKAL MICHAEL , HARTMANN RUDOLF , SCHEIFLINGER FRIEDRICH
IPC分类号： C12N9/64 , A61K38/36
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。

3. 发明申请

WO2008092643A3 IMPROVED FIX-MUTANT PROTEINS FOR HEMOPHILIA B TREATMENT 审中-公开
标题翻译：用于HEMOPHILIA B治疗的改进的固定蛋白
公开(公告)号：WO2008092643A3
公开(公告)日：2008-10-09
申请号：PCT/EP2008000684
申请日：2008-01-29
申请人： BAXTER INT , BAXTER HEALTHCARE SA , DOCKAL MICHAEL , HARTMANN RUDOLF , SCHEIFLINGER FRIEDRICH
发明人： DOCKAL MICHAEL , HARTMANN RUDOLF , SCHEIFLINGER FRIEDRICH
IPC分类号： C12N9/64
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。

4. 发明申请

WO2010071894A2 TFPI INHIBITORS AND METHODS OF USE 审中-公开
标题翻译： TFPI抑制剂及其使用方法
公开(公告)号：WO2010071894A2
公开(公告)日：2010-06-24
申请号：PCT/US2009069060
申请日：2009-12-21
申请人： BAXTER INT , BAXTER HEALTHCARE SA , 3B PHARMACEUTICALS GMBH , COSMIX MOLECULAR BIOLOG GMBH , DOCKAL MICHAEL , EHRLICH HARTMUT , SCHEIFLINGER FRIEDRICH , REIMER ULF , REINEKE ULRICH , POLAKOWSKI THOMAS , SCHNEIDER EBERHARD
发明人： DOCKAL MICHAEL , EHRLICH HARTMUT , SCHEIFLINGER FRIEDRICH , REIMER ULF , REINEKE ULRICH , POLAKOWSKI THOMAS , SCHNEIDER EBERHARD
IPC分类号： A61K38/10 , A61P7/02 , C07K7/08
CPC分类号： C07K14/4703 , A61K38/00 , A61K47/551 , A61K47/557 , A61K47/60 , C07K7/08 , C07K14/001
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）及其组合物的肽。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。

5. 发明申请

WO2010066869A2 PREPARATIONS BASED ON FIBRINOGEN AND SULFATED POLYSACCHARIDES 审中-公开
标题翻译：基于纤维素和硫化多糖的制备
公开(公告)号：WO2010066869A2
公开(公告)日：2010-06-17
申请号：PCT/EP2009066897
申请日：2009-12-11
申请人： BAXTER INT , BAXTER HEALTHCARE SA , DOCKAL MICHAEL , SCHEIFLINGER FRIEDRICH , HEDRICH HANS CHRISTIAN , TSCHETSCHKOWITSCH KLAUS
发明人： DOCKAL MICHAEL , SCHEIFLINGER FRIEDRICH , HEDRICH HANS CHRISTIAN , TSCHETSCHKOWITSCH KLAUS
IPC分类号： A61L26/00
CPC分类号： A61L24/106 , A61L24/043 , A61L2400/04
摘要： The present invention provides a preparation comprising fibrinogen and a sulfated polysaccharide as a one component composition or as a kit of parts comprising fibrinogen and sulfated polysaccharide as separated components. The present invention further provides a fibrin clot like structure obtainable by a defined process, a hemostatic patch, a two-component syringe system and various uses of the described preparations, fibrin clot like structures and patches.
摘要翻译：本发明提供一种包含纤维蛋白原和硫酸化多糖作为单组分组合物或作为包含纤维蛋白原和硫酸化多糖作为分离组分的试剂盒的制剂。本发明进一步提供可通过限定的方法获得的纤维蛋白凝块样结构，止血贴剂，双组分注射器系统以及所述制剂，纤维蛋白凝块样结构和贴剂的各种用途。

6. 发明申请

WO2010020423A3 METHODS FOR TREATING BLEEDING DISORDERS 审中-公开
标题翻译：治疗出血性疾病的方法
公开(公告)号：WO2010020423A3
公开(公告)日：2010-05-27
申请号：PCT/EP2009006082
申请日：2009-08-21
申请人： BAXTER HEALTHCARE SA , BAXTER INT , DOCKAL MICHAEL , SCHEIFLINGER FRIEDRICH , TURECEK PETER
发明人： DOCKAL MICHAEL , SCHEIFLINGER FRIEDRICH , TURECEK PETER
IPC分类号： A61K31/737 , A61K31/727 , A61P7/04
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 factor Xl-dependent blood coagulation enhancement in a subject in need of enhanced blood coagulation comprising administering a therapeutically effective amount of a composition comprising a non-anticoagulant sulfated polysaccharide (NASP) to the subject. A method of factor Xl-dependent blood coagulation enhancement in a subject in need of enhanced blood coagulation comprising: (i) selecting a subject that is not deficient for factor Xl; and (ii) administering a therapeutically effective amount of a composition comprising a non-anticoagulant sulfated polysaccharide (NASP) to the subject, wherein the NASP enhances blood coagulation in a factor Xl-dependent manner. A method of identifying a non-anticoagulant sulfated polysaccharide (NASP) which is capable of enhancing blood coagulation in dependence on FXI, the method comprising: a) combining a blood or plasma sample comprising activation competent FXI with a composition comprising 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 composition comprising the 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, wherein a decrease in the clotting time of the blood sample or an increase in peak thrombin or decrease in peak time of the plasma sample comprising activation competent FXI compared to the clotting time of the blood sample or peak thrombin or peak time of the plasma sample deficient in activation competent FXI is indicative of a NASP which is capable of enhancing blood coagulation in dependence on FXI.
摘要翻译：在需要增强血液凝固的受试者中增强因子XI依赖性血液凝固的方法，包括向受试者施用治疗有效量的包含非抗凝血剂硫酸化多糖（NASP）的组合物。一种在需要增强血液凝固的受试者中增强因子XI依赖性血液凝固的方法，包括：（i）选择对于因子XI不缺乏的受试者; 和（ii）将治疗有效量的包含非抗凝血剂硫酸化多糖（NASP）的组合物给予所述受试者，其中所述NASP以因子XI依赖性方式增强凝血。一种鉴定能够根据FXI增强血液凝固的非抗凝血硫酸化多糖（NASP）的方法，所述方法包括：a）将包含活化能力FXI的血液或血浆样品与包含硫酸化多糖的组合物混合并测量血液或血浆样品的凝血或凝血酶生成参数; b）将缺乏活化能力的FXI的相应血液或血浆样品与包含硫酸化多糖的组合物组合并测量血液或血浆样品的凝固或凝血酶生成参数; 和c）将在步骤（a）和（b）中确定的血液或血浆样品的凝血或凝血酶生成参数彼此比较，其中血样的凝固时间减少或峰值凝血酶增加或降低在包含活化能力FXI的血浆样品的峰值时间与血液样品或峰值凝血酶的凝固时间相比较或缺乏活化能力的血浆样品的峰值时间FXI表明NASP能够依赖于 FXI。

7. 发明申请

WO2011115712A3 TFPI INHIBITORS AND METHODS OF USE 审中-公开
标题翻译： TFPI抑制剂和使用方法
公开(公告)号：WO2011115712A3
公开(公告)日：2011-11-24
申请号：PCT/US2011024604
申请日：2011-02-11
申请人： BAXTER INT , BAXTER HEAL THCARE S A , DOCKAL MICHAEL , HARTMANN RUDOLF , FRIES MARKUS , SCHEIFLINGER FRIEDRICH , EHRLICH HARTMUT , REINEKE ULRICH , OSTERKAMP FRANK , POLAKOWSKI THOMAS
发明人： DOCKAL MICHAEL , HARTMANN RUDOLF , FRIES MARKUS , SCHEIFLINGER FRIEDRICH , EHRLICH HARTMUT , REINEKE ULRICH , OSTERKAMP FRANK , POLAKOWSKI THOMAS
IPC分类号： A61K38/18 , A61K38/16 , C40B40/10
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.
摘要翻译：本发明提供了结合组织因子途径抑制剂（TFPI）的肽，包括TFPI抑制肽及其组合物。所述肽可用于抑制TFPI，增强凝血因子缺陷受试者中的凝血酶形成，增加受试者的血块形成，治疗受试者中的凝血障碍，纯化TFPI并鉴定TFPI结合化合物。

8. 发明申请

WO2009083187A8 CHEMICALLY MODIFIED FACTOR IX 审中-公开
标题翻译：化学改性因子IX
公开(公告)号：WO2009083187A8
公开(公告)日：2009-09-17
申请号：PCT/EP2008010925
申请日：2008-12-19
申请人： BAXTER INT , BAXTER HEALTHCARE SA , TURECEK PETER , SCHEIFLINGER FRIEDRICH
发明人： TURECEK PETER , SCHEIFLINGER FRIEDRICH
IPC分类号： C12N9/64
CPC分类号： C12N9/644 , A61K38/00 , C12N9/96 , C12Y304/21022
摘要： The present invention discloses a chemically modified FIX, wherein the activation peptide region contains a covalently coupled water-soluble hydrophilic polymer.
摘要翻译：本发明公开了一种化学修饰的FIX，其中活化肽区含有共价偶联的水溶性亲水性聚合物。

9. 发明申请

WO2006071801A3 POLYMER-VON WILLEBRAND FACTOR-CONJUGATES 审中-公开
标题翻译： POLYMER-VON WILLEBRAND因子联合
公开(公告)号：WO2006071801A3
公开(公告)日：2007-08-16
申请号：PCT/US2005046879
申请日：2005-12-23
申请人： BAXTER INT , BAXTER HEALTHCARE SA , SCHEIFLINGER FRIEDRICH , TURECEK PETER , SIEKMANN JUERGEN
发明人： SCHEIFLINGER FRIEDRICH , TURECEK PETER , SIEKMANN JUERGEN
IPC分类号： A61K47/48
CPC分类号： C07K14/755 , A61K47/60 , C07K14/775
摘要： The present invention relates to a proteinaceous construc (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 said proteinaceous construc 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.
摘要翻译：本发明涉及包含血浆和/或重组血管性血友病因子（VWF）的蛋白质结构（也称为聚合物-WWF-缀合物），所述VWF与至少一种生理上可接受的聚合物分子结合，以及复合物所述蛋白质结构和至少一种因子VIII（FVIII）蛋白。生理上可接受的聚合物分子可以是例如聚乙二醇（PEG）或聚唾液酸（PSA）。此外，本发明涉及用于延长具有与FVIII或VWF中的至少一种的功能缺陷或缺陷相关的出血性疾病的哺乳动物的血液中VWF或FVIII的体内半衰期的方法。

10. 发明申请

WO2005025615A2 FACTOR IXa SPECIFIC ANTIBODIES DISPLAYING FACTOR VIIIa LIKE ACTIVITY 审中-公开
标题翻译：因子IXa特异性抗体显示因子VIIIa活性
公开(公告)号：WO2005025615A2
公开(公告)日：2005-03-24
申请号：PCT/EP2004009975
申请日：2004-09-07
申请人： BAXTER INT , BAXTER HEALTHCARE SA , SCHEIFLINGER FRIEDRICH , KERSCHBAUMER RANDOLF
发明人： SCHEIFLINGER FRIEDRICH , KERSCHBAUMER RANDOLF
IPC分类号： C07K16/36 , C07K16/40 , A61K39/395
CPC分类号： C07K16/36 , A61K2039/505 , C07K16/40
摘要： Ligands such as antibodies that can bind factor IX/factor IXa and increase the procoagulant activity of factor IXa (FIXa), pharmaceutical compositions containing such ligands, methods for treating patients afflicted with blood coagulation with such ligands, and a nucleic acid that encodes, or a cell that expresses such ligands, are provided.
摘要翻译：配体，例如可以结合因子IX /因子IXa并增加因子IXa（FIXa）的促凝活性的抗体，含有这种配体的药物组合物，用这种配体治疗患有凝血的患者的方法，以及编码或提供表达这种配体的细胞。

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