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1. 发明申请

WO2009140015A3 SITE-DIRECTED MODIFICATION OF FACTOR IX 审中-公开
公开(公告)号：WO2009140015A3
公开(公告)日：2009-11-19
申请号：PCT/US2009/040691
申请日：2009-04-15
申请人： BAYER HEALTHCARE LLC , BROOKS, Alan, R. , MURPHY, John, E. , SETO, Marian , JIANG, Xiaoqiao , KIEWLICH, David , PATEL, Chandra
发明人： BROOKS, Alan, R. , MURPHY, John, E. , SETO, Marian , JIANG, Xiaoqiao , KIEWLICH, David , PATEL, Chandra
IPC分类号： A61K38/48
摘要： The invention relates to modified Factor IX polypeptides such as Factor IX polypeptides with one or more introduced cysteine sites. The modified Factor IX polypeptides may be conjugated to a biocompatible polymer. The invention also relates to methods of making modified Factor IX polypeptides, and methods of using modified Factor IX polypeptides, for example, to treat patients afflicted with hemophilia B.

2. 发明申请

WO2009137254A2 MODIFIED FACTOR IX POLYPEPTIDES AND USES THEREOF 审中-公开
标题翻译：改性因子IX多糖及其用途
公开(公告)号：WO2009137254A2
公开(公告)日：2009-11-12
申请号：PCT/US2009/040813
申请日：2009-04-16
申请人： BAYER HEALTHCARE LLC , BAYER HEALTHCARE AG , BROOKS, Alan , MURPHY, John, E. , SETO, Marian , JIANG, Xiaoqiao , PATEL, Chandra , GRITZAN, Uwe , KIRCHNER, Kornelia , HAUPTS, Ulrich
发明人： BROOKS, Alan , MURPHY, John, E. , SETO, Marian , JIANG, Xiaoqiao , PATEL, Chandra , GRITZAN, Uwe , KIRCHNER, Kornelia , HAUPTS, Ulrich
IPC分类号： A61K38/36
CPC分类号： C12N9/644 , A61K38/00 , C12Y304/21022
摘要： The invention relates to modified Factor IX polypeptides such as Factor IX polypeptides with one or more introduced glycosylation sites. The modified Factor IX polypeptides may exhibit increased in vitro or in vivo stability such as a longer plasma half-life. The invention also relates to methods of making modified Factor IX polypeptides, and methods of using modified Factor IX polypeptides, for example, to treat patients afflicted with hemophilia B.
摘要翻译：本发明涉及修饰的因子IX多肽，例如具有一个或多个引入的糖基化位点的因子IX多肽。修饰的因子IX多肽可以表现出增加的体外或体内稳定性，例如更长的血浆半衰期。本发明还涉及制备修饰的因子IX多肽的方法，以及使用修饰的因子IX多肽的方法，例如治疗患有血友病B的患者。

3. 发明申请

WO2011014890A1 MODIFIED FACTOR IX POLYPEPTIDES AND USES THEREOF 审中-公开
标题翻译：改性因子IX多糖及其用途
公开(公告)号：WO2011014890A1
公开(公告)日：2011-02-03
申请号：PCT/US2010/044177
申请日：2010-08-02
申请人： BAYER HEALTHCARE LLC , BROOKS, Alan , PATEL, Chandra , JIANG, Xiaoqiao , GRITZAN, Uwe , APELER, Heiner , WANG, Jun
发明人： BROOKS, Alan , PATEL, Chandra , JIANG, Xiaoqiao , GRITZAN, Uwe , APELER, Heiner , WANG, Jun
IPC分类号： A61K38/36
CPC分类号： C12N9/644 , A61K38/00 , C12Y304/21022
摘要： The invention relates to modified Factor IX polypeptides such as Factor IX polypeptides with one or more amino acid substitutions. The invention also relates to methods of making modified Factor IX polypeptides, and methods of using modified Factor IX polypeptides, for example, to treat patients afflicted with hemophilia B.
摘要翻译：本发明涉及修饰的因子IX多肽，例如具有一个或多个氨基酸取代的因子IX多肽。本发明还涉及制备修饰的因子IX多肽的方法，以及使用修饰的因子IX多肽的方法，例如治疗患有血友病B的患者。

4. 发明申请

WO2014152530A1 VARIANT FACTOR VIII POLYPEPTIDES AND METHODS OF THEIR PRODUCTION AND USE 审中-公开
标题翻译：变异因子VIII多肽及其生产和使用方法
公开(公告)号：WO2014152530A1
公开(公告)日：2014-09-25
申请号：PCT/US2014/027443
申请日：2014-03-14
申请人： BAYER HEALTHCARE LLC
发明人： GRITZAN, Uwe , KRETSCHMER, Peter , LEONG, Lilley , PATEL, Chandra
IPC分类号： A61K35/14 , C07K1/00 , C07K14/00 , A61K38/37 , C07K14/755
CPC分类号： C07K14/755 , A61K38/37
摘要： This disclosure relates to variant Factor VIII polypeptides comprising an amino acid substitution at one or more positions within one or both of the thrombin cleavage site and the activation loop. In certain embodiments, the variant Factor VIII polypeptide comprises one or more amino acid substitutions within both the thrombin cleavage site and the activation loop. In further embodiments, the variant factor VIII polypeptide further comprises one or more amino acid substitutions within the A1-A2 domain interface and the A2-A3 domain interface. The present disclosure further relates to methods of producing and/or using such variant Factor VIII polypeptides; nucleic acids encoding the polypeptides; vectors and/or recombinant cells, tissues, or organisms containing such nucleic acids; and kits and pharmaceutical compositions containing such polypeptides and/or nucleic acids.
摘要翻译：本公开涉及在凝血酶切割位点和激活环之一或两者内的一个或多个位置处包含氨基酸取代的变体因子VIII多肽。在某些实施方案中，变体因子VIII多肽在凝血酶切割位点和活化环两者中都包含一个或多个氨基酸取代。在另外的实施方案中，变体因子VIII多肽还包含在A1-A2结构域界面和A2-A3结构域界面内的一个或多个氨基酸取代。本公开还涉及产生和/或使用这种变体因子VIII多肽的方法; 编码多肽的核酸; 载体和/或重组细胞，组织或含有此类核酸的生物; 以及含有这种多肽和/或核酸的试剂盒和药物组合物。

5. 发明公开

EP2282767A2 SITE-DIRECTED MODIFICATION OF FACTOR IX 审中-公开
标题翻译：因子IX的LOCAL LOOKING改性
公开(公告)号：EP2282767A2
公开(公告)日：2011-02-16
申请号：EP09747101.5
申请日：2009-04-15
申请人： Bayer HealthCare LLC
发明人： BROOKS, Alan, R. , MURPHY, John, E. , SETO, Marian , JIANG, Xiaoqiao , KIEWLICH, David , PATEL, Chandra
IPC分类号： A61K38/48
CPC分类号： C12N9/644 , A61K38/00 , A61K47/60 , C12Y304/21022
摘要： The invention relates to modified Factor IX polypeptides such as Factor IX polypeptides with one or more introduced cysteine sites. The modified Factor IX polypeptides may be conjugated to a biocompatible polymer. The invention also relates to methods of making modified Factor IX polypeptides, and methods of using modified Factor IX polypeptides, for example, to treat patients afflicted with hemophilia B.

6. 发明授权

EP2988758B1 VARIANT FACTOR VIII POLYPEPTIDES AND METHODS OF THEIR PRODUCTION AND USE 有权
标题翻译：变体因子VIII多肽及其生产和使用方法
公开(公告)号：EP2988758B1
公开(公告)日：2018-04-25
申请号：EP14770221.1
申请日：2014-03-14
申请人： Bayer HealthCare LLC
发明人： GRITZAN, Uwe , KRETSCHMER, Peter , LEONG, Lilley , PATEL, Chandra
IPC分类号： A61K35/14 , C07K1/00 , C07K14/00 , A61K38/37 , C07K14/755
CPC分类号： C07K14/755 , A61K38/37
摘要： This disclosure relates to variant Factor VIII polypeptides comprising an amino acid substitution at one or more positions within one or both of the thrombin cleavage site and the activation loop. In certain embodiments, the variant Factor VIII polypeptide comprises one or more amino acid substitutions within both the thrombin cleavage site and the activation loop. In further embodiments, the variant factor VIII polypeptide further comprises one or more amino acid substitutions within the A1-A2 domain interface and the A2-A3 domain interface. The present disclosure further relates to methods of producing and/or using such variant Factor VIII polypeptides; nucleic acids encoding the polypeptides; vectors and/or recombinant cells, tissues, or organisms containing such nucleic acids; and kits and pharmaceutical compositions containing such polypeptides and/or nucleic acids.

7. 发明公开

EP2988758A1 VARIANT FACTOR VIII POLYPEPTIDES AND METHODS OF THEIR PRODUCTION AND USE 有权
标题翻译： VARIANT因子VIII多肽和方法的生产和使用
公开(公告)号：EP2988758A1
公开(公告)日：2016-03-02
申请号：EP14770221.1
申请日：2014-03-14
申请人： Bayer HealthCare LLC
发明人： GRITZAN, Uwe , KRETSCHMER, Peter , LEONG, Lilley , PATEL, Chandra
IPC分类号： A61K35/14 , C07K1/00 , C07K14/00 , A61K38/37 , C07K14/755
CPC分类号： C07K14/755 , A61K38/37
摘要： This disclosure relates to variant Factor VIII polypeptides comprising an amino acid substitution at one or more positions within one or both of the thrombin cleavage site and the activation loop. In certain embodiments, the variant Factor VIII polypeptide comprises one or more amino acid substitutions within both the thrombin cleavage site and the activation loop. In further embodiments, the variant factor VIII polypeptide further comprises one or more amino acid substitutions within the A1-A2 domain interface and the A2-A3 domain interface. The present disclosure further relates to methods of producing and/or using such variant Factor VIII polypeptides; nucleic acids encoding the polypeptides; vectors and/or recombinant cells, tissues, or organisms containing such nucleic acids; and kits and pharmaceutical compositions containing such polypeptides and/or nucleic acids.

8. 发明公开

EP2288622A2 MODIFIED FACTOR IX POLYPEPTIDES AND USES THEREOF 审中-公开
标题翻译：修饰的因子IX多肽及其用途
公开(公告)号：EP2288622A2
公开(公告)日：2011-03-02
申请号：EP09743241.3
申请日：2009-04-16
申请人： Bayer HealthCare LLC , Bayer Schering Pharma Aktiengesellschaft
发明人： BROOKS, Alan , MURPHY, John, E. , SETO, Marian , JIANG, Xiaoqiao , PATEL, Chandra , GRITZAN, Uwe , KIRCHNER, Kornelia , HAUPTS, Ulrich
IPC分类号： C07K14/745
CPC分类号： C12N9/644 , A61K38/00 , C12Y304/21022
摘要： Disclosed are modified Factor IX polypeptides such as Factor IX polypeptides with one or more introduced glycosylation sites. The modified Factor IX polypeptides may exhibit increased in vitro or in vivo stability such as a longer plasma half-life. Also, methods are disclosed of making modified Factor IX polypeptides, and methods of using modified Factor IX polypeptides, for example, to treat patients afflicted with hemophilia B.

9. 发明公开

EP3427744A1 VARIANT FACTOR VIII POLYLEPTIDES AND METHODS OF THEIR PRODUCTION AND USE 审中-公开
公开(公告)号：EP3427744A1
公开(公告)日：2019-01-16
申请号：EP18159477.1
申请日：2014-03-14
申请人： Bayer Healthcare LLC
发明人： GRITZAN, Uwe , KRETSCHMER, Peter , LEONG, Lilley , PATEL, Chandra
IPC分类号： A61K35/14 , C07K1/00 , C07K14/00 , A61K38/37 , C07K14/755
摘要： This disclosure relates to variant Factor VIII polypeptides comprising an amino acid substitution at one or more positions within one or both of the thrombin cleavage site and the activation loop. In certain embodiments, the variant Factor VIII polypeptide comprises one or more amino acid substitutions within both the thrombin cleavage site and the activation loop. In further embodiments, the variant factor VIII polypeptide further comprises one or more amino acid substitutions within the A1-A2 domain interface and the A2-A3 domain interface. The present disclosure further relates to methods of producing and/or using such variant Factor VIII polypeptides; nucleic acids encoding the polypeptides; vectors and/or recombinant cells, tissues, or organisms containing such nucleic acids; and kits and pharmaceutical compositions containing such polypeptides and/or nucleic acids.

10. 发明公开

EP2461821A1 MODIFIED FACTOR IX POLYPEPTIDES AND USES THEREOF 审中-公开
标题翻译：修饰的因子IX多肽及其用途
公开(公告)号：EP2461821A1
公开(公告)日：2012-06-13
申请号：EP10805185.5
申请日：2010-08-02
申请人： Bayer HealthCare LLC
发明人： BROOKS, Alan , PATEL, Chandra , JIANG, Xiaoqiao , GRITZAN, Uwe , APELER, Heiner , WANG, Jun
IPC分类号： A61K38/36
CPC分类号： C12N9/644 , A61K38/00 , C12Y304/21022
摘要： The invention relates to modified Factor IX polypeptides such as Factor IX polypeptides with one or more amino acid substitutions. The invention also relates to methods of making modified Factor IX polypeptides, and methods of using modified Factor IX polypeptides, for example, to treat patients afflicted with hemophilia B.

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