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1. 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。

2. 发明专利

AU2011227714A1 TFPI inhibitors and methods of use 未知
公开(公告)号：AU2011227714A1
公开(公告)日：2012-09-20
申请号：AU2011227714
申请日：2011-02-11
申请人： BAXTER HEAL THCARE S A , BAXTER INT
发明人： DOCKAL MICHAEL , HARTMANN RUDOLF , FRIES MARKUS , SCHEIFLINGER FRIEDRICH , EHRLICH HARTMUT , REINEKE ULRICH , OSTERKAMP FRANK , POLAKOWSKI THOMAS
IPC分类号： A61K38/16 , A61K38/18 , C40B40/10
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.

3. 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。

4. 发明公开

EP2547355A4 TFPI INHIBITORS AND METHODS OF USE 有权转让
标题翻译： TFPI-HEMMER UND VERWENDUNGSVERFAHRENDAFÜR
公开(公告)号：EP2547355A4
公开(公告)日：2013-09-11
申请号：EP11756689
申请日：2011-02-11
申请人： BAXTER INT , BAXTER HEALTHCARE SA
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 , C07K14/81
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。

5. 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。

6. 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。

7. 发明专利

CA2793465C TFPI INHIBITORS AND METHODS OF USE 未知
公开(公告)号：CA2793465C
公开(公告)日：2022-06-14
申请号：CA2793465
申请日：2011-02-11
申请人： BAXTER INT , BAXTER HEALTHCARE SA
发明人： DOCKAL MICHAEL , HARTMANN RUDOLF , FRIES MARKUS , SCHEIFLINGER FRIEDRICH , EHRLICH HARTMUT , REINEKE ULRICH , OSTERKAMP FRANK , POLAKOWSKI THOMAS
IPC分类号： C07K7/08 , A61K38/16 , A61K38/18 , A61K38/36 , A61P7/04 , C07K7/06 , C07K14/81 , C07K17/00 , C07K19/00 , C40B30/04 , C40B40/10
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.

8. 发明专利

CA2674881A1 FVIII-INDEPENDENT FIX-MUTANT PROTEINS FOR HEMOPHILIA A TREATMENT 未知
公开(公告)号：CA2674881A1
公开(公告)日：2008-08-07
申请号：CA2674881
申请日：2008-01-29
申请人： BAXTER HEALTHCARE SA , BAXTER INT
发明人： SCHEIFLINGER FRIEDRICH , HARTMANN RUDOLF , DOCKAL MICHAEL
IPC分类号： C12N9/64 , A61K38/36
摘要： The present invention relates to recombinant blood coagulation factor IX (rFIX) mutants having factor VIII (FVIII) independent factor X (FX) activati on potential. Five full length FIX proteins with combinations of mutations o f amino acids important for functional activity of FIX and FIX wild type wer e cloned and expressed in HEK 293 cells. The proteins were tested by an acti vated partial thromboplastin time (aPTT) assay in FVIII-depleted plasma as w ell as in FVIII-inhibited patient plasma. In FVIII-depleted plasma functiona l activity of the FIX mutants was calculated as increased FVIII equivalent a ctivity. The mutant proteins had increased FVIII equivalent activity. In FVI II-inhibited patient plasma the FEIBA equivalent activity was calculated for analysis of FVIII independent FX activation potential. The proteins had als o increased FEIBA equivalent activity. Furthermore, the pre-activated FIX pr oteins had an increased activity in FIX-depleted plasma containing FVIII inh ibitors. Therefore these FIX mutants are alternatives as bypassing agents fo r treatment of FVIII inhibitor patients.

9. 发明专利

NZ623576A Tfpi inhibitors and methods of use 未知
公开(公告)号：NZ623576A
公开(公告)日：2015-11-27
申请号：NZ62357611
申请日：2011-02-11
申请人： BAXTER HEALTHCARE SA , BAXTER INT
发明人： HARTMANN RUDOLF , POLAKOWSKI THOMAS , OSTERKAMP FRANK , SCHEIFLINGER FRIEDRICH , FRIES MARKUS , EHRLICH HARTMUT , REINEKE ULRICH , DOCKAL MICHAEL
IPC分类号： A61K38/18 , A61K38/16 , C40B40/10
摘要： Disclosed is a peptide that binds TFPI comprising (a) an amino acid sequence having at least 85% identity to SEQ ID NO: 1334 or (b) an amino acid sequence comprising one or two substitution(s), deletion(s) or insertion(s) of the amino acid sequence of (a); wherein the sequence is as defined in the specification. Also disclosed is the use of the peptide for treating a subject suffering from a blood coagulation disorder or at risk of suffering from a blood coagulation disorder.

10. 发明专利

CA2674879A1 IMPROVED FIX-MUTANT PROTEINS FOR HEMOPHILIA B TREATMENT 未知
公开(公告)号：CA2674879A1
公开(公告)日：2008-08-07
申请号：CA2674879
申请日：2008-01-29
申请人： BAXTER HEALTHCARE SA , BAXTER INT
发明人： SCHEIFLINGER FRIEDRICH , HARTMANN RUDOLF , DOCKAL MICHAEL
IPC分类号： C12N9/64
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 functio nal activity of FIX and FIX wild type were cloned and expressed in HEK 293 c ells. The proteins were tested by an activated partial thromboplastin time ( aPTT) assays in FIX-depleted plasma. Two mutant proteins had increased speci fic 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.

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