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31. 发明申请

US20090215992A1 Dual variable domain immunoglobulin and uses thereof 审中-公开
公开(公告)号：US20090215992A1
公开(公告)日：2009-08-27
申请号：US11890215
申请日：2007-08-03
申请人： Chengbin Wu , Tariq Ghayur , Richard W. Dixon , Jochen G. Salfeld
发明人： Chengbin Wu , Tariq Ghayur , Richard W. Dixon , Jochen G. Salfeld
IPC分类号： C07K16/00 , C07K17/00
CPC分类号： C07K16/244 , A61K2039/505 , C07K16/245 , C07K16/2809 , C07K16/2887 , C07K16/468 , C07K2317/24 , C07K2317/56 , C07K2317/76 , C07K2317/92
摘要： The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

32. 发明授权

US06783756B2 Methods for regulating gene expression 失效
标题翻译：调节基因表达的方法
公开(公告)号：US06783756B2
公开(公告)日：2004-08-31
申请号：US09281674
申请日：1999-03-30
申请人： Hermann Bujard , Manfred Gossen , Jochen G. Salfeld , Jeffrey W. Voss
发明人： Hermann Bujard , Manfred Gossen , Jochen G. Salfeld , Jeffrey W. Voss
IPC分类号： A61K6300
CPC分类号： C12N15/62 , A01K67/0275 , A01K2217/05 , A01K2217/075 , C07K2319/09 , C07K2319/61 , C07K2319/71 , C07K2319/80 , C12N15/635 , C12N15/85 , C12N2830/006
摘要： A method for regulating expression of a tet operator-linked gene in a cell of a subject is disclosed. In one embodiment, the method involves introducing into the cell a nucleic acid molecule encoding a tetracycline-controllable transactivator (tTA), the tTA comprising a Tet repressor operably linked to a polypeptide which directly or indirectly activates transcription in eucaryotic cells; and modulating the concentration of a tetracycline, or analogue thereof, in the subject. Alternatively, in another embodiment, the method involves obtaining the cell from the subject, introducing into the cell a first nucleic acid molecule which operatively links a gene to at least one tet operator sequence, introducing into the cell a second nucleic acid molecule encoding a tTA, to form a modified cell, administering the modified cell to the subject, and modulating the concentration of a tetracycline, or analogue thereof, in the subject. The first and second nucleic acid molecule can be within a single molecule (e.g., in the same vector) or on separate molecules.
摘要翻译：公开了一种用于调节受试者细胞中tet操纵子连接基因表达的方法。在一个实施方案中，所述方法包括将编码四环素可控反式激活因子（tTA）的核酸分子引入细胞，所述tTA包含可操作地连接到直接或间接激活真核细胞中的转录的多肽的Tet阻遏物; 并调节受试者中四环素或其类似物的浓度。或者，在另一个实施方案中，所述方法包括从受试者获得细胞，向细胞中引入第一核酸分子，该第一核酸分子可操作地将基因连接至至少一个tet操纵子序列，将编码tTA的第二核酸分子，以形成修饰的细胞，向受试者施用修饰的细胞，并调节受试者中四环素或其类似物的浓度。第一和第二核酸分子可以在单分子内（例如，在同一载体中）或分开的分子上。

33. 发明授权

US06252136B1 Transgenic organisms having tetracycline-regulated transcriptional regulatory systems 有权
标题翻译：具有四环素调节转录调控系统的转基因生物
公开(公告)号：US06252136B1
公开(公告)日：2001-06-26
申请号：US09163269
申请日：1998-09-29
申请人： Hermann Bujard , Manfred Gossen , Jochen G. Salfeld , Jeffrey W. Voss
发明人： Hermann Bujard , Manfred Gossen , Jochen G. Salfeld , Jeffrey W. Voss
IPC分类号： C12N1509
CPC分类号： C12N15/62 , A01K67/0275 , A01K2217/05 , A01K2217/075 , C07K2319/09 , C07K2319/61 , C07K2319/71 , C07K2319/80 , C12N15/635 , C12N15/85 , C12N2830/006
摘要： Transgenic animals carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates in eucaryotic cells, and the second comprising a gene operably linked to a minimal promoter operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e.g., targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic animals having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked-gene of interest by administering tetracycline or a tetracycline analogue to an animal of the invention are also disclosed. The regulatory system of the invention allows for conditional inactivation or modulation of expression of a gene of interest in a host cell or animal.
摘要翻译：携带两个转基因的转基因动物，第一编码包含直接或间接在真核细胞中活化的tet阻遏物和多肽的反式激活因子融合蛋白，第二编码包含与可操作地连接至少一个tet操纵子的最小启动子可操作地连接的基因序列。还公开了通过同源重组将编码本发明的反式激活物的多核苷酸序列整合到第二靶DNA分子内的预定位置的分离的DNA分子（例如靶向载体）。通过同源重组将具有整合在染色体中预定位置的本发明的DNA分子的转基因动物也包括在本发明中。还公开了通过向本发明的动物施用四环素或四环素类似物来调节所述目的基因的表达的方法。本发明的调节系统允许在宿主细胞或动物中有条件地失活或调控感兴趣的基因的表达。

34. 发明授权

US5650298A Tight control of gene expression in eucaryotic cells by tetracycline-responsive promoters 失效
标题翻译：通过四环素响应启动子对真核细胞中基因表达的严格控制
公开(公告)号：US5650298A
公开(公告)日：1997-07-22
申请号：US260452
申请日：1994-06-14
申请人： Hermann Bujard , Manfred Gossen , Jochen G. Salfeld , Jeffrey W. Voss
发明人： Hermann Bujard , Manfred Gossen , Jochen G. Salfeld , Jeffrey W. Voss
IPC分类号： A01K67/027 , A61K48/00 , C07K14/00 , C12N5/08 , C12N5/10 , C12N15/00 , C12N15/09 , C12N15/31 , C12N15/62 , C12N15/63 , C12N15/85 , C12R1/91 , C12P21/00 , C07H21/04
CPC分类号： A01K67/0275 , C12N15/62 , C12N15/635 , C12N15/85 , A01K2217/05 , A01K2217/075 , C07K2319/09 , C07K2319/61 , C07K2319/71 , C07K2319/80 , C12N2830/006
摘要： Transgenic animals carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates in eucaryotic cells, and the second comprising a gene operably linked to a minimal promoter operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e.g., targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic animals having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked-gene of interest by administering tetracycline or a tetracycline analogue to an animal of the invention are also disclosed. The regulatory system of the invention allows for conditional inactivation or modulation of expression of a gene of interest in a host cell or animal.
摘要翻译：携带两个转基因的转基因动物，第一编码包含直接或间接在真核细胞中活化的tet阻遏物和多肽的反式激活因子融合蛋白，第二编码包含与可操作地连接至少一个tet操纵子的最小启动子可操作地连接的基因序列。还公开了通过同源重组将编码本发明的反式激活物的多核苷酸序列整合到第二靶DNA分子内的预定位置的分离的DNA分子（例如靶向载体）。通过同源重组将具有整合在染色体中预定位置的本发明的DNA分子的转基因动物也包括在本发明中。还公开了通过向本发明的动物施用四环素或四环素类似物来调节所述目的基因的表达的方法。本发明的调节系统允许在宿主细胞或动物中有条件地失活或调控感兴趣的基因的表达。

35. 发明申请

US20130115224A1 METHODS OF TREATING DISORDERS USING HUMAN ANTIBODIES THAT BIND HUMAN TNFalpha 审中-公开
标题翻译：使用人类TNFα的人类抗体治疗疾病的方法
公开(公告)号：US20130115224A1
公开(公告)日：2013-05-09
申请号：US13736931
申请日：2013-01-08
申请人： Jochen G. SALFELD , Deborah J. Allen , Zehra Kaymakcalan , Boris Labkovsky , John A. Mankovich , Brian T. McGuinness , Andrew J. Roberts , Paul Sakorafas , Hendricus R.j.m. Hoogenboom , David Schoenhaut , Tristan J. Vaughan , Michael White , Alison J. Wilton
发明人： Jochen G. SALFELD , Deborah J. Allen , Zehra Kaymakcalan , Boris Labkovsky , John A. Mankovich , Brian T. McGuinness , Andrew J. Roberts , Paul Sakorafas , Hendricus R.j.m. Hoogenboom , David Schoenhaut , Tristan J. Vaughan , Michael White , Alison J. Wilton
IPC分类号： C07K16/24
CPC分类号： C07K16/241 , A61K38/00 , A61K2039/505 , C07K2317/21 , C07K2317/56 , C07K2317/565 , Y02A50/412 , Y10S424/81
摘要： Human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor α (hTNFα) are disclosed. These antibodies have high affinity for hTNFα (e.g., Kd=10−8 M or less), a slow off rate for hTNFα dissociation (e.g., Koff=10−3 sec−1 or less) and neutralize hTNFα activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hTNFα and for inhibiting hTNFα activity, e.g., in a human subject suffering from a disorder in which hTNFα activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.
摘要翻译：公开了特异性结合人肿瘤坏死因子α（hTNFα）的人抗体，优选重组人抗体。这些抗体对hTNFalpha（例如，Kd = 10-8M或更低）具有高亲和力，hTNFalpha解离的缓慢速率（例如，Koff = 10-3秒-1或更低），并在体外和体内中和hTNFalpha活性。本发明的抗体可以是全长抗体或其抗原结合部分。本发明的抗体或抗体部分可用于检测hTNFα和抑制hTNFα活性，例如在患有hTNFα活性有害的病症的人类受试者中。用于表达本发明的重组人抗体的核酸，载体和宿主细胞以及合成重组人抗体的方法也包括在本发明中。

36. 发明申请

US20130004416A1 Dual Variable Domain Immunoglobulin and Uses Thereof 审中-公开
公开(公告)号：US20130004416A1
公开(公告)日：2013-01-03
申请号：US13601774
申请日：2012-08-31
申请人： Chengbin WU , Tariq Ghayur , Richard W. Dixon , Jochen G. Salfeld
发明人： Chengbin WU , Tariq Ghayur , Richard W. Dixon , Jochen G. Salfeld
IPC分类号： A61K39/395 , A61K49/00 , C12P21/02 , C12N9/96 , C12N5/10 , C12N1/21 , C12N1/15 , C12N1/19 , C12N1/11 , C12N15/63 , C07K16/00 , A61P21/02 , A61P29/00 , A61P23/00 , A61P21/00 , A61P31/04 , A61P17/06 , A61P37/06 , A61P25/24 , A61P25/18 , A61P11/06 , A61P19/02 , A61P1/00 , A61P3/10 , A61P37/08 , A61P17/00 , A61P41/00 , A61P9/10 , A61P13/12 , A61P31/12 , A61P31/00 , A61P25/16 , A61P25/28 , A61P9/00 , A61P11/00 , A61P7/06 , A61P15/00 , A61P19/04 , A61P1/16 , A61P25/32 , A61P35/00 , A61P35/02 , A61P31/18 , A61P25/06 , A61P25/00 , A61P19/10 , A61K51/00
CPC分类号： C07K16/468 , A61K39/3955 , A61K45/06 , A61K47/42 , A61K47/6803 , A61K51/1093 , A61K2039/505 , C07K16/22 , C07K16/24 , C07K16/241 , C07K16/244 , C07K16/245 , C07K16/2809 , C07K16/2887 , C07K16/2896 , C07K16/40 , C07K16/46 , C07K16/467 , C07K2317/24 , C07K2317/31 , C07K2317/51 , C07K2317/522 , C07K2317/56 , C07K2317/64 , C07K2317/76 , Y02A50/386 , Y02A50/41 , Y02A50/412 , Y02A50/58
摘要： The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

37. 发明申请

US20120219564A1 Human Antibodies That Bind Human TNFalpha 失效
标题翻译：绑定人类TNFα的人类抗体
公开(公告)号：US20120219564A1
公开(公告)日：2012-08-30
申请号：US13466892
申请日：2012-05-08
申请人： JOCHEN G. SALFELD , DEBORAH J. ALLEN , HENDRICUS R.J.M. HOOGENBOOM , ZEHRA KAYMAKCALAN , BORIS LABKOVSKY , JOHN A. MANKOVICH , BRIAN T. MCGUINNESS , ANDREW J. ROBERTS , PAUL SAKORAFAS , DAVID SCHOENHAUT , TRISTAN J. VAUGHAN , MICHAEL WHITE , ALISON J. WILTON
发明人： JOCHEN G. SALFELD , DEBORAH J. ALLEN , HENDRICUS R.J.M. HOOGENBOOM , ZEHRA KAYMAKCALAN , BORIS LABKOVSKY , JOHN A. MANKOVICH , BRIAN T. MCGUINNESS , ANDREW J. ROBERTS , PAUL SAKORAFAS , DAVID SCHOENHAUT , TRISTAN J. VAUGHAN , MICHAEL WHITE , ALISON J. WILTON
IPC分类号： A61K39/395 , A61P29/00 , A61P37/06 , A61P31/00 , A61P31/04 , A61P33/06 , A61P31/18 , A61P31/22 , A61P35/00 , A61P11/00 , A61P1/00 , A61P9/00 , A61P9/10 , A61P19/08 , A61P1/16 , A61P7/00 , A61P17/02 , C07K16/24
CPC分类号： C07K16/241 , A61K38/00 , A61K2039/505 , C07K2317/21 , C07K2317/56 , C07K2317/565 , C07K2317/92 , Y02A50/412 , Y10S424/80 , Y10S424/81 , Y10S530/868
摘要： Human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor α (hTNFα) are disclosed. These antibodies have high affinity for hTNFα (e.g., Kd=10−8 M or less), a slow off rate for hTNFα dissociation (e.g., Koff=10−3 sec−1 or less) and neutralize hTNFα activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hTNFα and for inhibiting hTNFα activity, e.g., in a human subject suffering from a disorder in which hTNFα activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.
摘要翻译：公开了特异性结合人肿瘤坏死因子α（hTNFα）的人抗体，优选重组人抗体。这些抗体对hTNFα具有高亲和力（例如，Kd = 10-8M或更低），hTNFα解离的缓慢速率（例如，Koff = 10-3秒-1或更低），并在体外和体内中和hTNFα活性。本发明的抗体可以是全长抗体或其抗原结合部分。本发明的抗体或抗体部分可用于检测hTNFα和抑制hTNFα活性，例如在患有hTNFα活性有害的病症的人类受试者中。用于表达本发明的重组人抗体的核酸，载体和宿主细胞以及合成重组人抗体的方法也包括在本发明中。

38. 发明申请

US20110123544A1 HUMAN ANTIBODIES THAT BIND HUMAN IL-12 AND METHODS FOR PRODUCING 审中-公开
标题翻译：人类IL-12的人体抗体和生产方法
公开(公告)号：US20110123544A1
公开(公告)日：2011-05-26
申请号：US12910461
申请日：2010-10-22
申请人： Jochen G. Salfeld , Michael Roguska , Michael Paskind , Subhashis Banerjee , Daniel Edward Tracey , Michael White , Zehra Edward Kaymakcalan , Boris Labkovsky , Paul Sakorafas , Geertuida M. Veldman , Amy Venturini , Angela Widom , Stuart Friedrich , Nicholas W. Warne , Angela Kantor , John Gawain Elvin , Alexander Robert Duncan , Elaine Joy Derbyshire , Sara Carmen , Stephen Smith , Thor Las Holtet , Sarah Leila Du Fou
发明人： Jochen G. Salfeld , Michael Roguska , Michael Paskind , Subhashis Banerjee , Daniel Edward Tracey , Michael White , Zehra Edward Kaymakcalan , Boris Labkovsky , Paul Sakorafas , Geertuida M. Veldman , Amy Venturini , Angela Widom , Stuart Friedrich , Nicholas W. Warne , Angela Kantor , John Gawain Elvin , Alexander Robert Duncan , Elaine Joy Derbyshire , Sara Carmen , Stephen Smith , Thor Las Holtet , Sarah Leila Du Fou
IPC分类号： C07K16/24 , A61K39/395 , G01N33/566 , C07K14/54 , A61P19/02 , A61P37/00 , A61P9/10 , A61P13/12 , A61P25/28 , A61P25/16 , A61P31/00 , A61P7/06 , A61P3/10 , A61P9/00 , A61P35/04 , A61P17/06
CPC分类号： C07K16/244 , A61K2039/505 , C07K2317/21 , C07K2317/30 , C07K2317/33 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C07K2317/92
摘要： Human antibodies, preferably recombinant human antibodies, that specifically bind to human interleukin-12 (hIL-12) are disclosed. Preferred antibodies have high affinity for hIL-12 and neutralize hIL-12 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hIL-12 and for inhibiting hIL-12 activity, e.g., in a human subject suffering from a disorder in which hIL-12 activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.
摘要翻译：公开了特异性结合人白细胞介素-12（hIL-12）的人抗体，优选重组人抗体。优选的抗体对hIL-12具有高亲和力，并在体外和体内中和hIL-12活性。本发明的抗体可以是全长抗体或其抗原结合部分。本发明的抗体或抗体部分可用于检测hIL-12和抑制hIL-12活性，例如在患有hIL-12活性有害的病症的人类受试者中。用于表达本发明的重组人抗体的核酸，载体和宿主细胞以及合成重组人抗体的方法也包括在本发明中。

39. 发明申请

US20100047239A1 Dual variable domain immunoglobulin and uses thereof 有权
标题翻译：双可变域免疫球蛋白及其用途
公开(公告)号：US20100047239A1
公开(公告)日：2010-02-25
申请号：US12459624
申请日：2009-07-02
申请人： Chengbin Wu , Tariq Ghayur , Richard W. Dixon , Jochen G. Salfeld
发明人： Chengbin Wu , Tariq Ghayur , Richard W. Dixon , Jochen G. Salfeld
IPC分类号： A61K39/395 , C07K16/18 , C07H21/04 , C12N15/63 , C12N1/21 , C12N1/15 , C12N1/19 , C12P21/06
CPC分类号： C07K16/468 , A61K39/3955 , A61K45/06 , A61K47/42 , A61K47/48384 , A61K47/6803 , A61K51/1093 , A61K2039/505 , C07K16/22 , C07K16/24 , C07K16/241 , C07K16/244 , C07K16/245 , C07K16/2809 , C07K16/2887 , C07K16/2896 , C07K16/40 , C07K16/46 , C07K16/467 , C07K2317/24 , C07K2317/31 , C07K2317/51 , C07K2317/522 , C07K2317/56 , C07K2317/64 , C07K2317/76 , Y02A50/386 , Y02A50/41 , Y02A50/412 , Y02A50/58
摘要： The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.
摘要翻译：本发明涉及工程化的多价和多特异性结合蛋白，制备方法，特别涉及其用于预防和/或治疗急性和慢性炎症和其它疾病的用途。

40. 发明授权

US07588761B2 Human antibodies that bind human TNFα 失效
标题翻译：结合人TNFα的人抗体
公开(公告)号：US07588761B2
公开(公告)日：2009-09-15
申请号：US11233252
申请日：2005-09-21
申请人： Jochen G. Salfeld , Deborah J. Allen , Hendricus R. J. M. Hoogenboom , Zehra Kaymakcalan , Boris Labkovsky , John A. Mankovich , Brian T. McGuinness , Andrew J. Roberts , Paul Sakorafas , David Schoenhaut , Tristan J. Vaughan , Michael White , Alison J. Wilton
发明人： Jochen G. Salfeld , Deborah J. Allen , Hendricus R. J. M. Hoogenboom , Zehra Kaymakcalan , Boris Labkovsky , John A. Mankovich , Brian T. McGuinness , Andrew J. Roberts , Paul Sakorafas , David Schoenhaut , Tristan J. Vaughan , Michael White , Alison J. Wilton
IPC分类号： A61K39/395 , C07K16/24
CPC分类号： C07K16/241 , A61K38/00 , A61K2039/505 , C07K2317/21 , C07K2317/56 , C07K2317/565 , C07K2317/92 , Y02A50/412 , Y10S424/80 , Y10S424/81 , Y10S530/868
摘要： Human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor α (hTNFα) are disclosed. These antibodies have high affinity for hTNFα (e.g., Kd=10−8 M or less), a slow off rate for hTNFα dissociation (e.g., Koff=10−3 sec−1 or less) and neutralize hTNFα activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hTNFα and for inhibiting hTNFα activity, e.g., in a human subject suffering from a disorder in which hTNFα activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.
摘要翻译：公开了特异性结合人肿瘤坏死因子α（hTNFα）的人抗体，优选重组人抗体。这些抗体对hTNFalpha（例如，Kd = 10-8M或更低）具有高亲和力，hTNFalpha解离的缓慢速率（例如，Koff = 10-3秒-1或更低），并在体外和体内中和hTNFalpha活性。本发明的抗体可以是全长抗体或其抗原结合部分。本发明的抗体或抗体部分可用于检测hTNFα和抑制hTNFα活性，例如在患有hTNFα活性有害的病症的人类受试者中。用于表达本发明的重组人抗体的核酸，载体和宿主细胞以及合成重组人抗体的方法也包括在本发明中。

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