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1. 发明申请

US20120178107A1 HUMAN ANTIBODIES THAT BIND HUMAN TNFalpha 失效
标题翻译：人类TNFα的人类抗体
公开(公告)号：US20120178107A1
公开(公告)日：2012-07-12
申请号：US13340805
申请日：2011-12-30
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： G01N33/566 , C07K16/24 , C12N9/96
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）并且在体外和体内中和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。

2. 发明授权

US08414894B2 Human antibodies that bind human TNFα and methods of using same 失效
标题翻译：结合人TNFα的人抗体及其使用方法
公开(公告)号：US08414894B2
公开(公告)日：2013-04-09
申请号：US13340805
申请日：2011-12-30
申请人： Jochen G. Salfeld , John A. Mankovich , Deborah J. Allen , Hendricus R.J.M. Hoogenboom , Boris Labkovsky , Brian T. McGuinness , Paul Sakorafas , Michael White , Alison J. Wilton , Zehra Kaymakcalan , Andrew J. Roberts , David Schoenhaut , Tristan J. Vaughan
发明人： Jochen G. Salfeld , John A. Mankovich , Deborah J. Allen , Hendricus R.J.M. Hoogenboom , Boris Labkovsky , Brian T. McGuinness , Paul Sakorafas , Michael White , Alison J. Wilton , Zehra Kaymakcalan , Andrew J. Roberts , David Schoenhaut , Tristan J. Vaughan
IPC分类号： A61K39/395 , C07K16/00 , G01N33/53
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。

3. 发明申请

US20100040604A1 HUMAN ANTIBODIES THAT BIND HUMAN TNFalpha 失效
标题翻译：人类TNFα的人类抗体
公开(公告)号：US20100040604A1
公开(公告)日：2010-02-18
申请号：US12578487
申请日：2009-10-13
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
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。

4. 发明申请

US20100016557A1 HUMAN ANTIBODIES THAT BIND HUMAN TNFalpha 有权
标题翻译：人类TNFα的人类抗体
公开(公告)号：US20100016557A1
公开(公告)日：2010-01-21
申请号：US12401469
申请日：2009-03-10
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： C07K16/24 , C07H21/04
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。

5. 发明申请

US20110287971A1 MULTI-CHAIN EUKARYOTIC DISPLAY VECTORS AND USES THEREOF 有权
公开(公告)号：US20110287971A1
公开(公告)日：2011-11-24
申请号：US13170362
申请日：2011-06-28
申请人： Simon E. Hufton , Hendricus R.J.M. Hoogenboom
发明人： Simon E. Hufton , Hendricus R.J.M. Hoogenboom
IPC分类号： C40B30/04 , C40B40/02
CPC分类号： C12N15/1037 , C12N15/85 , C12N2795/00043 , C12N2800/108 , C12N2830/002 , C12N2840/20 , C40B40/02 , G01N33/554
摘要： A eukaryotic expression vector capable of displaying a multi-chain polypeptide on the surface of a host cell is provided, such that the biological activity of the multi-chain polypeptide is exhibited at the surface of the host cell. Such a vector allows for the display of complex biologically active polypeptides, e.g., biologically active multi-chain polypeptides such as immunoglobulin Fab fragments. The present invention describes and enables the successful display of a multi-chain polypeptide on the surface of a eukaryotic host cell. Preferred vectors are described for expressing the chains of a multi-chain polypeptide in a host cell separately and independently (e.g., under separate vector control elements, and/or on separate expression vectors, thus forming a matched vector set). The use of such matched vector sets provides flexibility and versatility in the generation of eukaryotic display libraries, for example the ability to generate and to display multi-chain polypeptides by combining and recombining vectors that express variegations of the individual chains of a multi-chain polypeptide. Entire repertoires of novel chain combinations can be devised using such vector sets.

6. 发明申请

US20110281360A1 MULTI-CHAIN EUKARYOTIC DISPLAY VECTORS AND USES THEREOF 有权
公开(公告)号：US20110281360A1
公开(公告)日：2011-11-17
申请号：US13170448
申请日：2011-06-28
申请人： Simon E. Hufton , Hendricus R.J.M. Hoogenboom
发明人： Simon E. Hufton , Hendricus R.J.M. Hoogenboom
IPC分类号： C12N15/04
CPC分类号： C12N15/1037 , C12N15/85 , C12N2795/00043 , C12N2800/108 , C12N2830/002 , C12N2840/20 , C40B40/02 , G01N33/554
摘要： A eukaryotic expression vector capable of displaying a multi-chain polypeptide on the surface of a host cell is provided, such that the biological activity of the multi-chain polypeptide is exhibited at the surface of the host cell. Such a vector allows for the display of complex biologically active polypeptides, e.g., biologically active multi-chain polypeptides such as immunoglobulin Fab fragments. The present invention describes and enables the successful display of a multi-chain polypeptide on the surface of a eukaryotic host cell. Preferred vectors are described for expressing the chains of a multi-chain polypeptide in a host cell separately and independently (e.g., under separate vector control elements, and/or on separate expression vectors, thus forming a matched vector set). The use of such matched vector sets provides flexibility and versatility in the generation of eukaryotic display libraries, for example the ability to generate and to display multi-chain polypeptides by combining and recombining vectors that express variegations of the individual chains of a multi-chain polypeptide. Entire repertoires of novel chain combinations can be devised using such vector sets.

7. 发明申请

US20110190159A1 MULTI-CHAIN EUKARYOTIC DISPLAY VECTORS AND USES THEREOF 有权
标题翻译：多链显示矢量及其用途
公开(公告)号：US20110190159A1
公开(公告)日：2011-08-04
申请号：US13073657
申请日：2011-03-28
申请人： Simon E. Hufton , Hendricus R.J.M. Hoogenboom
发明人： Simon E. Hufton , Hendricus R.J.M. Hoogenboom
IPC分类号： C40B30/04 , C40B50/06 , C40B30/00
CPC分类号： C12N15/1037 , C12N15/85 , C12N2795/00043 , C12N2800/108 , C12N2830/002 , C12N2840/20 , C40B40/02 , G01N33/554
摘要： A eukaryotic expression vector capable of displaying a multi-chain polypeptide on the surface of a host cell is provided, such that the biological activity of the multi-chain polypeptide is exhibited at the surface of the host cell. Such a vector allows for the display of complex biologically active polypeptides, e.g., biologically active multi-chain polypeptides such as immunoglobulin Fab fragments. The present invention describes and enables the successful display of a multi-chain polypeptide on the surface of a eukaryotic host cell. Preferred vectors are described for expressing the chains of a multi-chain polypeptide in a host cell separately and independently (e.g., under separate vector control elements, and/or on separate expression vectors, thus forming a matched vector set). The use of such matched vector sets provides flexibility and versatility in the generation of eukaryotic display libraries, for example the ability to generate and to display multi-chain polypeptides by combining and recombining vectors that express variegations of the individual chains of a multi-chain polypeptide. Entire repertoires of novel chain combinations can be devised using such vector sets.
摘要翻译：提供能够在宿主细胞表面上显示多链多肽的真核表达载体，使得多链多肽的生物学活性显示在宿主细胞的表面。这种载体允许显示复杂的生物活性多肽，例如生物活性多链多肽，例如免疫球蛋白Fab片段。本发明描述并使得能够在真核宿主细胞的表面上成功显示多链多肽。描述了优选的载体，用于在宿主细胞中分别且独立地（例如，在单独的载体控制元件下和/或在分开的表达载体上，从而形成匹配的载体集）表达多链多肽的链。使用这种匹配的载体集提供了在真核生物显示文库的产生中的灵活性和多功能性，例如通过组合和重组表达多链多肽的各个链多态的载体来产生和显示多链多肽的能力。可以使用这样的矢量集来设计新的链组合的全部曲目。

8. 发明申请

US20110281761A1 MULTI-CHAIN EUKARYOTIC DISPLAY VECTORS AND USES THEREOF 有权
公开(公告)号：US20110281761A1
公开(公告)日：2011-11-17
申请号：US13170438
申请日：2011-06-28
申请人： Simon E. Hufton , Hendricus R.J.M. Hoogenboom
发明人： Simon E. Hufton , Hendricus R.J.M. Hoogenboom
IPC分类号： C40B30/04
CPC分类号： C12N15/1037 , C12N15/85 , C12N2795/00043 , C12N2800/108 , C12N2830/002 , C12N2840/20 , C40B40/02 , G01N33/554
摘要： A eukaryotic expression vector capable of displaying a multi-chain polypeptide on the surface of a host cell is provided, such that the biological activity of the multi-chain polypeptide is exhibited at the surface of the host cell. Such a vector allows for the display of complex biologically active polypeptides, e.g., biologically active multi-chain polypeptides such as immunoglobulin Fab fragments. The present invention describes and enables the successful display of a multi-chain polypeptide on the surface of a eukaryotic host cell. Preferred vectors are described for expressing the chains of a multi-chain polypeptide in a host cell separately and independently (e.g., under separate vector control elements, and/or on separate expression vectors, thus forming a matched vector set). The use of such matched vector sets provides flexibility and versatility in the generation of eukaryotic display libraries, for example the ability to generate and to display multi-chain polypeptides by combining and recombining vectors that express variegations of the individual chains of a multi-chain polypeptide. Entire repertoires of novel chain combinations can be devised using such vector sets.

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