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1. 发明授权

US09290561B2 Factor VIII, von Willebrand factor or complexes thereof with prolonged in vivo half-life 有权
标题翻译：因子VIII，血管性血友病因子或其复合物具有延长的体内半衰期
公开(公告)号：US09290561B2
公开(公告)日：2016-03-22
申请号：US14028869
申请日：2013-09-17
申请人： Thomas Weimer , Stefan Schulte , Hubert Metzner , Ulrich Kronthaler , Holger Lind , Wiegand Lang
发明人： Thomas Weimer , Stefan Schulte , Hubert Metzner , Ulrich Kronthaler , Holger Lind , Wiegand Lang
IPC分类号： A61K38/37 , A61K38/36 , A61K38/38 , A61K38/16 , A61K35/14 , C07K1/00 , C07K14/76 , C07K14/755 , A61K38/00
CPC分类号： C07K14/76 , A61K38/00 , C07K14/755 , C07K2319/31
摘要： The present invention relates to modified nucleic acid sequences coding for coagulation factor VIII (FVIII) and for von Willebrand factor (VWF) as well as complexes thereof and their derivatives, recombinant expression vectors containing such nucleic acid sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives coded for by said nucleic acid sequences which recombinant polypeptides and derivatives do have biological activities together with prolonged in vivo half-life and/or improved in vivo recovery compared to the unmodified wild-type protein. The invention also relates to corresponding FVIII sequences that result in improved expression yield. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives. The invention also relates to a transfer vector for use in human gene therapy, which comprises such modified nucleic acid sequences.
摘要翻译：本发明涉及编码凝血因子VIII（FVIII）和von Willebrand因子（VWF）的修饰的核酸序列及其复合物及其衍生物，含有此类核酸序列的重组表达载体，用这种重组表达转化的宿主细胞载体，重组多肽和由所述核酸序列编码的衍生物，所述重组多肽和衍生物与未修饰的野生型蛋白质相比具有生物活性以及延长的体内半衰期和/或改善的体内恢复。本发明还涉及导致表达产量提高的相应FVIII序列。本发明还涉及制备这些重组蛋白及其衍生物的方法。本发明还涉及用于人基因治疗的转移载体，其包含这种修饰的核酸序列。

2. 发明申请

US20140072561A1 FACTOR VIII, VON WILLEBRAND FACTOR OR COMPLEXES THEREOF WITH PROLONGED IN VIVO HALF-LIFE 审中-公开
标题翻译：因子VIII，VON WILLEBRAND因子或其复合物与生殖健康生活息息相关
公开(公告)号：US20140072561A1
公开(公告)日：2014-03-13
申请号：US14028869
申请日：2013-09-17
申请人： Thomas Weimer , Stefan Schulte , Hubert Metzner , Ulrich Kronthaler , Holger Lind , Wiegand Lang
发明人： Thomas Weimer , Stefan Schulte , Hubert Metzner , Ulrich Kronthaler , Holger Lind , Wiegand Lang
IPC分类号： C07K14/76 , C07K14/755
CPC分类号： C07K14/76 , A61K38/00 , C07K14/755 , C07K2319/31
摘要： The present invention relates to modified nucleic acid sequences coding for coagulation factor VIII (FVIII) and for von Willebrand factor (VWF) as well as complexes thereof and their derivatives, recombinant expression vectors containing such nucleic acid sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives coded for by said nucleic acid sequences which recombinant polypeptides and derivatives do have biological activities together with prolonged in vivo half-life and/or improved in vivo recovery compared to the unmodified wild-type protein. The invention also relates to corresponding FVIII sequences that result in improved expression yield. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives. The invention also relates to a transfer vector for use in human gene therapy, which comprises such modified nucleic acid sequences.
摘要翻译：本发明涉及编码凝血因子VIII（FVIII）和von Willebrand因子（VWF）的修饰的核酸序列及其复合物及其衍生物，含有此类核酸序列的重组表达载体，用这种重组表达转化的宿主细胞载体，重组多肽和由所述核酸序列编码的衍生物，所述重组多肽和衍生物与未修饰的野生型蛋白质相比具有生物活性以及延长的体内半衰期和/或改善的体内恢复。本发明还涉及导致表达产量提高的相应FVIII序列。本发明还涉及制备这些重组蛋白及其衍生物的方法。本发明还涉及用于人基因治疗的转移载体，其包含这种修饰的核酸序列。

3. 发明申请

US20110183907A1 FACTOR VIII, VON WILLEBRAND FACTOR OR COMPLEXES THEREOF WITH PROLONGED IN VIVO HALF-LIFE 有权
标题翻译：因子VIII，VON WILLEBRAND因子或其复合物与生殖健康生活息息相关
公开(公告)号：US20110183907A1
公开(公告)日：2011-07-28
申请号：US13000938
申请日：2009-06-24
申请人： Thomas Weimer , Stefan Schulte , Hubert Metzner , Ulrich Kronthaler , Holger Lind , Wiegand Lang
发明人： Thomas Weimer , Stefan Schulte , Hubert Metzner , Ulrich Kronthaler , Holger Lind , Wiegand Lang
IPC分类号： A61K38/37 , C07K14/755 , C07K14/745 , C07K19/00 , C07H21/00 , C12N15/63 , C12N5/10 , C12P21/00 , A61K38/36 , A61K31/7088 , A61K48/00 , C07K1/107 , A61P7/04
CPC分类号： C07K14/76 , A61K38/00 , C07K14/755 , C07K2319/31
摘要： The present invention relates to modified nucleic acid sequences coding for coagulation factor VIII (FVIII) and for von Willebrand factor (VWF) as well as complexes thereof and their derivatives, recombinant expression vectors containing such nucleic acid sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives coded for by said nucleic acid sequences which recombinant polypeptides and derivatives do have biological activities together with prolonged in vivo half-life and/or improved in vivo recovery compared to the unmodified wild-type protein. The invention also relates to corresponding FVIII sequences that result in improved expression yield. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives. The invention also relates to a transfer vector for use in human gene therapy, which comprises such modified nucleic acid sequences.
摘要翻译：本发明涉及编码凝血因子VIII（FVIII）和von Willebrand因子（VWF）的修饰的核酸序列及其复合物及其衍生物，含有此类核酸序列的重组表达载体，用这种重组表达转化的宿主细胞载体，重组多肽和由所述核酸序列编码的衍生物，所述重组多肽和衍生物与未修饰的野生型蛋白质相比具有生物活性以及延长的体内半衰期和/或改善的体内恢复。本发明还涉及导致表达产量提高的相应FVIII序列。本发明还涉及制备这些重组蛋白及其衍生物的方法。本发明还涉及用于人基因治疗的转移载体，其包含这种修饰的核酸序列。

4. 发明授权

US08575104B2 Factor VIII, von willebrand factor or complexes thereof with prolonged in vivo half-life 有权
标题翻译：因子VIII，血管性血友病因子或其复合物具有延长的体内半衰期
公开(公告)号：US08575104B2
公开(公告)日：2013-11-05
申请号：US13000938
申请日：2009-06-24
申请人： Thomas Weimer , Stefan Schulte , Hubert Metzner , Ulrich Kronthaler , Holger Lind , Wiegand Lang
发明人： Thomas Weimer , Stefan Schulte , Hubert Metzner , Ulrich Kronthaler , Holger Lind , Wiegand Lang
IPC分类号： A61K38/37 , A61K38/36 , A61K38/16 , A61K35/14 , C07K1/00 , C12N5/00
CPC分类号： C07K14/76 , A61K38/00 , C07K14/755 , C07K2319/31
摘要： The present invention relates to modified nucleic acid sequences coding for coagulation factor VIII (FVIII) and for von Willebrand factor (VWF) as well as complexes thereof and their derivatives, recombinant expression vectors containing such nucleic acid sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives coded for by said nucleic acid sequences which recombinant polypeptides and derivatives do have biological activities together with prolonged in vivo half-life and/or improved in vivo recovery compared to the unmodified wild-type protein. The invention also relates to corresponding FVIII sequences that result in improved expression yield. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives. The invention also relates to a transfer vector for use in human gene therapy, which comprises such modified nucleic acid sequences.
摘要翻译：本发明涉及编码凝血因子VIII（FVIII）和von Willebrand因子（VWF）的修饰的核酸序列及其复合物及其衍生物，含有此类核酸序列的重组表达载体，用这种重组表达转化的宿主细胞载体，重组多肽和由所述核酸序列编码的衍生物，所述重组多肽和衍生物与未修饰的野生型蛋白质相比具有生物活性以及延长的体内半衰期和/或改善的体内恢复。本发明还涉及导致表达产量提高的相应FVIII序列。本发明还涉及制备这些重组蛋白及其衍生物的方法。本发明还涉及用于人基因治疗的转移载体，其包含这种修饰的核酸序列。

5. 发明授权

US08765915B2 Modified coagulation factor VIIa with extended half-life 有权
标题翻译：改性凝血因子Ⅶa具有延长的半衰期
公开(公告)号：US08765915B2
公开(公告)日：2014-07-01
申请号：US12223616
申请日：2007-02-03
申请人： Thomas Weimer , Stefan Schulte , Ulrich Kronthaler , Wiegand Lang , Uwe Liebing , Wilfried Wormsbächer
发明人： Thomas Weimer , Stefan Schulte , Ulrich Kronthaler , Wiegand Lang , Uwe Liebing , Wilfried Wormsbächer
IPC分类号： A61K38/35 , A61K38/38 , C07K14/745 , C07K14/76 , C07K14/765 , C12N9/64 , A61K38/00
CPC分类号： A61K38/4846 , A61K9/0019 , A61K38/00 , A61K38/385 , C07K14/76 , C07K2319/00 , C07K2319/31 , C12N9/6437 , C12N9/96 , C12N15/62 , C12Y304/21021
摘要： The present invention relates to the fields of Factor VII (FVII) and Factor VIIa (FVIIa) albumin linked polypeptides. More specifically, the invention relates to cDNA sequences coding for human Factor VII and Factor VIIa and derivatives genetically fused to a cDNA coding for human serum albumin which may be linked by oligonucleotides which code for intervening peptidic linkers such encoded derivatives exhibiting improved stability and extended functional plasma half-life, recombinant expression vectors containing such cDNA sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives which do have biological activities of the unmodified wild type protein but having improved stability and prolonged shelf-life and processes for the manufacture of such recombinant proteins and their derivatives. The invention also covers a transfer vector for use in human gene therapy, which comprises such modified DNA sequences.
摘要翻译：本发明涉及因子VII（FVII）和因子VIIa（FVIIa）白蛋白连接多肽的领域。更具体地，本发明涉及编码人因子VII和因子VIIa的cDNA序列和与编码人血清白蛋白的cDNA遗传融合的衍生物，其可以通过寡核苷酸连接，所述寡核苷酸编码干扰肽接头，这种编码的衍生物表现出改进的稳定性和延长的功能血浆半衰期，含有这些cDNA序列的重组表达载体，用这种重组表达载体转化的宿主细胞，确实具有未修饰的野生型蛋白的生物活性但具有改善的稳定性和延长的保存期限的重组多肽和衍生物制备这些重组蛋白及其衍生物。本发明还涵盖用于人基因治疗的转移载体，其包含这种修饰的DNA序列。

6. 发明申请

US20090298760A1 Modified Coagulation Factor VIIa With Extended Half-Life 有权
标题翻译：具有延长半衰期的改性凝血因子VIIa
公开(公告)号：US20090298760A1
公开(公告)日：2009-12-03
申请号：US12223616
申请日：2007-02-03
申请人： Thomas Weimer , Stefan Schulte , Ulrich Kronthaler , Wiegand Lang , Uwe Liebing , Wilfried Wormsbächer
发明人： Thomas Weimer , Stefan Schulte , Ulrich Kronthaler , Wiegand Lang , Uwe Liebing , Wilfried Wormsbächer
IPC分类号： A61K38/38 , C12P21/04 , C12N5/00 , C12N15/63 , A61K31/7088 , C07K14/76 , C07H21/04
CPC分类号： A61K38/4846 , A61K9/0019 , A61K38/00 , A61K38/385 , C07K14/76 , C07K2319/00 , C07K2319/31 , C12N9/6437 , C12N9/96 , C12N15/62 , C12Y304/21021
摘要： The present invention relates to the fields of Factor VII (FVII) and Factor VIIa (FVIIa) albumin linked polypeptides. More specifically, the invention relates to cDNA sequences coding for human Factor VII and Factor VIIa and derivatives genetically fused to a cDNA coding for human serum albumin which may be linked by oligonucleotides which code for intervening peptidic linkers such encoded derivatives exhibiting improved stability and extended functional plasma half-life, recombinant expression vectors containing such cDNA sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives which do have biological activities of the unmodified wild type protein but having improved stability and prolonged shelf-life and processes for the manufacture of such recombinant proteins and their derivatives. The invention also covers a transfer vector for use in human gene therapy, which comprises such modified DNA sequences.
摘要翻译：本发明涉及因子VII（FVII）和因子VIIa（FVIIa）白蛋白连接多肽的领域。更具体地，本发明涉及编码人因子VII和因子VIIa的cDNA序列和与编码人血清白蛋白的cDNA遗传融合的衍生物，其可以通过寡核苷酸连接，所述寡核苷酸编码干扰肽接头，这种编码的衍生物表现出改进的稳定性和延长的功能血浆半衰期，含有这些cDNA序列的重组表达载体，用这种重组表达载体转化的宿主细胞，确实具有未修饰的野生型蛋白的生物活性但具有改善的稳定性和延长的保存期限的重组多肽和衍生物制备这些重组蛋白及其衍生物。本发明还涵盖用于人基因治疗的转移载体，其包含这种修饰的DNA序列。

7. 发明申请

US20130337532A1 THERAPEUTIC POLYPEPTIDES WITH INCREASED IN VIVO RECOVERY 审中-公开
标题翻译：治疗性多糖在体重恢复中增加
公开(公告)号：US20130337532A1
公开(公告)日：2013-12-19
申请号：US13921815
申请日：2013-06-19
申请人： Thomas Weimer , Hubert Metzner , Stefan Schulte , Wiegand Lang , Wilfried Wormsbacher
发明人： Thomas Weimer , Hubert Metzner , Stefan Schulte , Wiegand Lang , Wilfried Wormsbacher
IPC分类号： C12N9/64
CPC分类号： C12N9/644 , A61K47/62 , A61K47/643 , C07K2319/31 , C12N9/14 , C12N9/6424 , C12N9/6437
摘要： The present invention relates to the field of modified therapeutic polypeptides with increased in vivo recovery compared to their non-modified parent polypeptide. For example, the invention relates to fusions of therapeutic polypeptides with recovery enhancing polypeptides connected directly or optionally connected by a linker peptide.
摘要翻译：本发明涉及与其未修饰的亲本多肽相比具有增加的体内恢复的修饰的治疗性多肽的领域。例如，本发明涉及治疗性多肽与通过连接肽直接连接或任选连接的恢复增强多肽的融合。

8. 发明申请

US20100222554A1 Method of Increasing the In Vivo Recovery of Therapeutic Polypeptides 审中-公开
标题翻译：增加治疗性多肽体内复原的方法
公开(公告)号：US20100222554A1
公开(公告)日：2010-09-02
申请号：US12226188
申请日：2007-04-02
申请人： Thomas Weimer , Hubert Metzner , Stefan Schulte , Wiegand Lang , Wilfried Wormsbächer
发明人： Thomas Weimer , Hubert Metzner , Stefan Schulte , Wiegand Lang , Wilfried Wormsbächer
IPC分类号： C07K1/107
CPC分类号： C12N9/644 , A61K47/62 , A61K47/643 , C07K2319/31 , C12N9/14 , C12N9/6424 , C12N9/6437
摘要： The present invention relates to the field of modified therapeutic polypeptides with increased in vivo recovery compared to their non-modified parent polypeptide. I.e., the invention relates to fusions of therapeutic polypeptides with recovery enhancing polypeptides connected directly or optionally connected by a linker peptide.
摘要翻译：本发明涉及与其未修饰的亲本多肽相比具有增加的体内恢复的修饰的治疗性多肽的领域。即，本发明涉及治疗性多肽与通过连接肽直接或任选连接的恢复增强多肽的融合。

9. 发明授权

US08283319B2 Therapeutic application of Kazal-type serine protease inhibitors 有权
标题翻译： Kazal型丝氨酸蛋白酶抑制剂的治疗应用
公开(公告)号：US08283319B2
公开(公告)日：2012-10-09
申请号：US12526758
申请日：2008-02-11
申请人： Stefan Schulte , Ulrich Kronthaler , Stefan Schmidbauer , Thomas Weimer , Kay Hofmann
发明人： Stefan Schulte , Ulrich Kronthaler , Stefan Schmidbauer , Thomas Weimer , Kay Hofmann
IPC分类号： A61K38/16 , C07K14/00
CPC分类号： C07K14/8135 , A61K38/00 , A61K47/64 , A61K47/643
摘要： The present invention relates to the therapeutic application of the Kazal-type serine protease inhibitor Infestin or domains thereof or modified Kazal-type serine protease inhibitors based on Infestin homologs, which prevent the formation and/or stabilization of three-dimensional arterial or venous thrombi by interfering with proteins involved in activation of the so-called intrinsic coagulation pathway. The present invention also relates to the use of Kazal-type serine protease inhibitors or fragments thereof or modified Kazal-type serine protease inhibitors in the treatment or prophylaxis of a condition or disorder related to arterial thrombus formation, i.e. stroke or myocardial infarction, inflammation, complement activation, fibrinolysis, angiogenesis and/or diseases linked to pathological kinin formation such as hypotonic shock, edema including hereditary angioedema, bacterial infections, arthritis, pancreatitis, or articular gout, Disseminated Intravasal Coagulation (DIC) and sepsis.
摘要翻译：本发明涉及基于Infestin同系物的Kazal型丝氨酸蛋白酶抑制剂Infestin或其结构域或修饰的Kazal型丝氨酸蛋白酶抑制剂的治疗应用，其防止三维动脉或静脉血栓的形成和/或稳定化干扰参与所谓的内在凝血途径活化的蛋白质。本发明还涉及Kazal型丝氨酸蛋白酶抑制剂或其片段或修饰的Kazal型丝氨酸蛋白酶抑制剂在治疗或预防与动脉血栓形成有关的病症或障碍的应用，即中风或心肌梗塞，炎症，补体活化，纤维蛋白溶解，血管发生和/或与病理激肽形成相关的疾病，如低渗休克，水肿，包括遗传性血管性水肿，细菌感染，关节炎，胰腺炎或关节痛风，弥散性内皮内凝血（DIC）和败血症。

10. 发明申请

US20100279923A1 THERAPEUTIC APPLICATION OF KAZAL-TYPE SERINE PROTEASE INHIBITORS 有权
标题翻译：卡氏型丝氨酸蛋白酶抑制剂的治疗应用
公开(公告)号：US20100279923A1
公开(公告)日：2010-11-04
申请号：US12526758
申请日：2008-02-11
申请人： Stefan Schulte , Ulrich Kronthaler , Stefan Schmidbauer , Thomas Weimer , Kay Hofmann
发明人： Stefan Schulte , Ulrich Kronthaler , Stefan Schmidbauer , Thomas Weimer , Kay Hofmann
IPC分类号： A61K38/55 , C07K14/00 , C07K14/76 , C07K16/00 , A61P5/00 , A61P35/00 , A61P9/00 , A61P9/10 , C12P21/06
CPC分类号： C07K14/8135 , A61K38/00 , A61K47/64 , A61K47/643
摘要： The subject of the present invention is, in the most general aspect, the therapeutic application of the Kazal-type serine protease inhibitor Infestin or domains thereof or modified Kazal-type serine protease inhibitors based on Infestin homologs, which prevent the formation and/or stabilization of three-dimensional arterial or venous thrombi by interfering with proteins involved in activation of the so-called intrinsic coagulation pathway. In particular the present invention relates to the use of said Kazal-type serine protease inhibitors or fragments thereof or modified Kazal-type serine protease inhibitors, in the treatment or prophylaxis of a condition or disorder related to arterial thrombus formation, i. e. stroke or myocardial infarction, inflammation, complement activation, fibrinolysis, angiogenesis and/or diseases linked to pathological kinin formation such as hypotonic shock, edema including hereditary angioedema, bacterial infections, arthritis, pancreatitis, or articular gout, Disseminated Intravasal Coagulation (DIC) and sepsis.
摘要翻译：本发明的主题在最一般的方面是基于Infestin同系物的Kazal型丝氨酸蛋白酶抑制剂Infestin或其结构域或修饰的Kazal型丝氨酸蛋白酶抑制剂的治疗应用，其防止形成和/或稳定化通过干扰参与所谓的内在凝血途径的激活的蛋白质的三维动脉或静脉血栓。特别地，本发明涉及所述Kazal型丝氨酸蛋白酶抑制剂或其片段或修饰的Kazal型丝氨酸蛋白酶抑制剂在治疗或预防与动脉血栓形成相关的病症或障碍中的用途， e。中风或心肌梗塞，炎症，补体激活，纤维蛋白溶解，血管生成和/或与病理激肽形成相关的疾病，例如低渗休克，包括遗传性血管性水肿，细菌感染，关节炎，胰腺炎或关节痛风的水肿，弥散性内皮内凝血（DIC）和败血症

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