公开(公告)号：JP2003177130A

公开(公告)日：2003-06-27

申请号：JP2002259017

申请日：2002-09-04

Applicant: BASF AG

Inventor： SALFELD JOCHEN G ,  ALLEN DEBORAH J ,  KAYMAKCALAN ZEHRA

IPC: C12N15/09 ,  A61K31/00 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4178 ,  A61K31/505 ,  A61K31/517 ,  A61K31/52 ,  A61K31/529 ,  A61K31/57 ,  A61K31/573 ,  A61K31/675 ,  A61K38/00 ,  A61K38/04 ,  A61K38/16 ,  A61K39/39 ,  A61K39/395 ,  A61P1/00 ,  A61P1/04 ,  A61P1/16 ,  A61P3/10 ,  A61P7/00 ,  A61P7/04 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/16 ,  A61P13/12 ,  A61P17/00 ,  A61P17/02 ,  A61P19/02 ,  A61P19/06 ,  A61P25/00 ,  A61P27/02 ,  A61P29/02 ,  A61P31/00 ,  A61P31/04 ,  A61P31/12 ,  A61P31/18 ,  A61P33/06 ,  A61P35/00 ,  A61P35/04 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  A61P39/02 ,  C07K16/24 ,  C12N1/21 ,  C12N5/10 ,  C12P21/08 ,  G01N33/53 ,  G01N33/543 ,  G01N33/564 ,  G01N33/576 ,  G01N33/68

Abstract: PROBLEM TO BE SOLVED: To provide human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor (TNF) α. SOLUTION: A method for inhibiting the human TNF α activity, including contact between the human TNF α and an antibody so as to inhibit the human TNF α activity is provided, wherein the antibody is the isolated human antibody dissociating from the human TNF α at rate constants of K d below 1×10 -8 M and K off below 1×10 -3 s -1 or its antigen-binding portion, both of which are measured by surface plasmon resonance, and the antibody neutralizes the cytotoxicity of the human TNF α at IC 50 below 1×10 -7 M by the standard in vitro L929 assay. COPYRIGHT: (C)2003,JPO

公开(公告)号：WO9429442A3

公开(公告)日：1995-02-02

申请号：PCT/US9406734

申请日：1994-06-14

Applicant: BASF AG ,  BUJARD HERMANN ,  GOSSEN MANFRED ,  SALFELD JOCHEN G ,  VOSS JEFFREY W

Inventor： BUJARD HERMANN ,  GOSSEN MANFRED ,  SALFELD JOCHEN G ,  VOSS JEFFREY W

IPC: A01K67/027 ,  A61K48/00 ,  C07K14/00 ,  C12N5/08 ,  C12N5/10 ,  C12N15/00 ,  C12N15/09 ,  C12N15/31 ,  C12N15/62 ,  C12N15/63 ,  C12N15/85 ,  C12R1/91 ,  C12N1/15 ,  C12N1/19 ,  C12N15/12 ,  C12N15/90

CPC classification number: A01K67/0275 ,  A01K2217/05 ,  A01K2217/075 ,  C07K2319/09 ,  C07K2319/61 ,  C07K2319/71 ,  C07K2319/80 ,  C12N15/62 ,  C12N15/635 ,  C12N15/85 ,  C12N2830/006

Abstract: 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 promotor 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.

Abstract translation: 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关注的tet操纵子连接基因的表达的方法。 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。

公开(公告)号：BG107537A

公开(公告)日：2003-09-30

申请号：BG10753703

申请日：1998-09-08

Applicant: BASF AG

Inventor： SALFELD JOCHEN G ,  ALLEN DEBORAH J ,  KAYMAKCALAN ZEHRA ,  LABKOVSKY BORIS ,  MANKOVICH JOHN A ,  MCGUINNESS BRIAN T ,  ROBERTS ANDREW J ,  SAKORAFAS PAUL ,  HOOGENBOOM HENDRICUS R ,  SCHOENHAUT DAVID ,  VAUGHAN TRISTAN J ,  WHITE MICHAEL ,  WILTON ALISON J

IPC: C12N15/09 ,  A61K31/00 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4178 ,  A61K31/505 ,  A61K31/517 ,  A61K31/52 ,  A61K31/529 ,  A61K31/57 ,  A61K31/573 ,  A61K31/675 ,  A61K38/00 ,  A61K38/04 ,  A61K38/16 ,  A61K39/39 ,  A61K39/395 ,  A61P1/00 ,  A61P1/04 ,  A61P1/16 ,  A61P3/10 ,  A61P7/00 ,  A61P7/04 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/16 ,  A61P13/12 ,  A61P17/00 ,  A61P17/02 ,  A61P19/02 ,  A61P19/06 ,  A61P25/00 ,  A61P27/02 ,  A61P29/02 ,  A61P31/00 ,  A61P31/04 ,  A61P31/12 ,  A61P31/18 ,  A61P33/06 ,  A61P35/00 ,  A61P35/04 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  A61P39/02 ,  C07K16/24 ,  C12N1/21 ,  C12N5/10 ,  C12P21/08 ,  G01N33/53 ,  G01N33/543 ,  G01N33/564 ,  G01N33/576 ,  G01N33/68 ,  C12N15/13 ,  C12N15/64

Abstract: The invention relates to a method for the inhibition of human TNFalpha activity by using isolated human antibody or its antigen-connection part. This property to inhibit TNFalpha finds application to produce medicaments for the treatment of diseases wherein the hTHFalpha activity is detrimental. 99 claims, 9 figures

公开(公告)号：AU722077B2

公开(公告)日：2000-07-20

申请号：AU2122997

申请日：1997-02-10

Applicant: BASF AG

Inventor： SALFELD JOCHEN G ,  ALLEN DEBORAH J ,  KAYMAKCALAN ZEHRA ,  LABKOVSKY BORIS ,  MANKOVICH JOHN A ,  MCGUINESS BRIAN T ,  ROBERTS ANDREW J ,  SAKORAFAS PAUL ,  HOOGENBOOM HENDRICUS R J M ,  SCHOENHAUT DAVID ,  VAUGHAN TRISTAN J ,  WHITE MICHAEL ,  WILTON ALISON J

IPC: C12N15/09 ,  A61K31/00 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4178 ,  A61K31/505 ,  A61K31/517 ,  A61K31/52 ,  A61K31/529 ,  A61K31/57 ,  A61K31/573 ,  A61K31/675 ,  A61K38/00 ,  A61K38/04 ,  A61K38/16 ,  A61K39/39 ,  A61K39/395 ,  A61P1/00 ,  A61P1/04 ,  A61P1/16 ,  A61P3/10 ,  A61P7/00 ,  A61P7/04 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/16 ,  A61P13/12 ,  A61P17/00 ,  A61P17/02 ,  A61P19/02 ,  A61P19/06 ,  A61P25/00 ,  A61P27/02 ,  A61P29/02 ,  A61P31/00 ,  A61P31/04 ,  A61P31/12 ,  A61P31/18 ,  A61P33/06 ,  A61P35/00 ,  A61P35/04 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  A61P39/02 ,  C07K16/24 ,  C12N1/21 ,  C12N5/10 ,  C12P21/08 ,  G01N33/53 ,  G01N33/543 ,  G01N33/564 ,  G01N33/576 ,  G01N33/68 ,  C12N15/13 ,  C12N15/64

Abstract: 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.

公开(公告)号：CZ247698A3

公开(公告)日：1998-11-11

申请号：CZ247698

申请日：1997-02-10

Applicant: BASF AG

Inventor： SALFELD JOCHEN G ,  ALLEN DEBORA J ,  KAYMAKCALAN ZEHRA ,  LABKOVSKY BORIS ,  MANKOVICH JOHN A ,  MCGUINESS BRIAN T ,  ROBERTS ANDREW J ,  SAKORAFAS PAUL ,  HOOGENBOOM HENDRICUS R J M ,  SCHOENHAUT DAVID ,  VAUGHAN TRISTAN J ,  WHITE MICHAEL ,  WILTON ALISON J

IPC: C12N15/09 ,  A61K31/00 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4178 ,  A61K31/505 ,  A61K31/517 ,  A61K31/52 ,  A61K31/529 ,  A61K31/57 ,  A61K31/573 ,  A61K31/675 ,  A61K38/00 ,  A61K38/04 ,  A61K38/16 ,  A61K39/39 ,  A61K39/395 ,  A61P1/00 ,  A61P1/04 ,  A61P1/16 ,  A61P3/10 ,  A61P7/00 ,  A61P7/04 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/16 ,  A61P13/12 ,  A61P17/00 ,  A61P17/02 ,  A61P19/02 ,  A61P19/06 ,  A61P25/00 ,  A61P27/02 ,  A61P29/02 ,  A61P31/00 ,  A61P31/04 ,  A61P31/12 ,  A61P31/18 ,  A61P33/06 ,  A61P35/00 ,  A61P35/04 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  A61P39/02 ,  C07K16/24 ,  C12N1/21 ,  C12N5/10 ,  C12P21/08 ,  G01N33/53 ,  G01N33/543 ,  G01N33/564 ,  G01N33/576 ,  G01N33/68 ,  C12N15/13 ,  C12N15/64

Abstract: 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.

公开(公告)号：MX9806347A

公开(公告)日：1998-10-31

申请号：MX9806347

申请日：1998-08-06

Applicant: BASF AG

Inventor： SALFELD JOCHEN G ,  ALLEN DEBORAH J ,  HOOGENBOOM HENDRICUS R J M ,  KAYMAKCALAN ZEHRA ,  LABKOVSKY BORIS ,  MANKOVICH JOHN A ,  MCGUINNESS BRIAN T ,  ROBERTS ANDREW J ,  SAKORAFAS PAUL

IPC: C12N15/09 ,  A61K31/00 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4178 ,  A61K31/505 ,  A61K31/517 ,  A61K31/52 ,  A61K31/529 ,  A61K31/57 ,  A61K31/573 ,  A61K31/675 ,  A61K38/00 ,  A61K38/04 ,  A61K38/16 ,  A61K39/39 ,  A61K39/395 ,  A61P1/00 ,  A61P1/04 ,  A61P1/16 ,  A61P3/10 ,  A61P7/00 ,  A61P7/04 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/16 ,  A61P13/12 ,  A61P17/00 ,  A61P17/02 ,  A61P19/02 ,  A61P19/06 ,  A61P25/00 ,  A61P27/02 ,  A61P29/02 ,  A61P31/00 ,  A61P31/04 ,  A61P31/12 ,  A61P31/18 ,  A61P33/06 ,  A61P35/00 ,  A61P35/04 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  A61P39/02 ,  C07K16/24 ,  C12N1/21 ,  C12N5/10 ,  C12P21/08 ,  G01N33/53 ,  G01N33/543 ,  G01N33/564 ,  G01N33/576 ,  G01N33/68 ,  C12N15/13 ,  C12N15/64 ,  C12N05/10 ,  C12N01/21

Abstract: Se dan a conocer anticuerpos humanos, de preferencia anticuerpos humanos recombinantes que se ligan específicamente a un facor de necrosis de tumor humano alfa(hTNFalfa). Estos anticuerpos tienen gran afinidad para hTNFalfa (v.g. Kd = 10-8 M o menos), un régimen de disociacion lento para disociacion de hTNFalfa (v.g. Koff = 10-3 sec-1 o menos) y neutralizan la actividad de hTNFalfa in vitro e in vivo. Un anticuerpo de la invencion puede ser un anticuerpo de longitud completa o una porcion de ligazon de antígeno del mismo. Los anticuerpos o porciones de anticuerpo de la invencion son utiles para detectar hTNFalfa y para inhibir la actividad de hTNFalfa v.g. en pacientes humanos que padecen de un trastorno en el cual es perjudicial la actividad de hTNFalfa. Los ácidos nucleicos, vectores y células huésped para expresar los anticuerpos humanos recombinantes de la invencion y los métodos para sintetizar los anticuerpos humanos recombinantes, también quedan abarcados mediante la invencion.

公开(公告)号：NO20040052L

公开(公告)日：1998-10-07

申请号：NO20040052

申请日：2004-01-07

Applicant: BASF AG

Inventor： SALFELD JOCHEN G ,  ALLEN DEBORAH J ,  HOOGENBOOM HENDRICUS R J M ,  KAYMAKCALAN ZEHRA ,  LABKOVSKY BORIS ,  MANKOVICH JOHN A ,  MCGUINNES BRIAN T ,  ROBERTS ANDREW J ,  SAKORAFAS PAUL ,  SCHOENHAUT DAVID ,  VAUGHAN TRISTAN J ,  WHITE MICHAEL ,  WILTON ALISON JANE

IPC: C12N15/09 ,  A61K31/00 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4178 ,  A61K31/505 ,  A61K31/517 ,  A61K31/52 ,  A61K31/529 ,  A61K31/57 ,  A61K31/573 ,  A61K31/675 ,  A61K38/00 ,  A61K38/04 ,  A61K38/16 ,  A61K39/39 ,  A61K39/395 ,  A61P1/00 ,  A61P1/04 ,  A61P1/16 ,  A61P3/10 ,  A61P7/00 ,  A61P7/04 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/16 ,  A61P13/12 ,  A61P17/00 ,  A61P17/02 ,  A61P19/02 ,  A61P19/06 ,  A61P25/00 ,  A61P27/02 ,  A61P29/02 ,  A61P31/00 ,  A61P31/04 ,  A61P31/12 ,  A61P31/18 ,  A61P33/06 ,  A61P35/00 ,  A61P35/04 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  A61P39/02 ,  C07K16/24 ,  C12N1/21 ,  C12N5/10 ,  C12P21/08 ,  G01N33/53 ,  G01N33/543 ,  G01N33/564 ,  G01N33/576 ,  G01N33/68

Abstract: 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.

公开(公告)号：NO20026202A

公开(公告)日：1998-10-07

申请号：NO20026202

申请日：2002-12-23

Applicant: BASF AG

Inventor： SALFELD JOCHEN G ,  ALLEN DEBORAH J ,  HOOGENBOOM HENDRICUS R J M ,  KAYMAKCALAN ZEHRA ,  LABKOVSKY BORIS ,  MANKOVICH JOHN A ,  MCGUINNES BRIAN T ,  ROBERTS ANDREW J ,  SAKORAFAS PAUL ,  SCHOENHAUT DAVID ,  VAUGHAN TRISTAN J ,  WHITE MICHAEL ,  WILTON ALISON JANE

IPC: C12N15/09 ,  A61K31/00 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4178 ,  A61K31/505 ,  A61K31/517 ,  A61K31/52 ,  A61K31/529 ,  A61K31/57 ,  A61K31/573 ,  A61K31/675 ,  A61K38/00 ,  A61K38/04 ,  A61K38/16 ,  A61K39/39 ,  A61K39/395 ,  A61P1/00 ,  A61P1/04 ,  A61P1/16 ,  A61P3/10 ,  A61P7/00 ,  A61P7/04 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/16 ,  A61P13/12 ,  A61P17/00 ,  A61P17/02 ,  A61P19/02 ,  A61P19/06 ,  A61P25/00 ,  A61P27/02 ,  A61P29/02 ,  A61P31/00 ,  A61P31/04 ,  A61P31/12 ,  A61P31/18 ,  A61P33/06 ,  A61P35/00 ,  A61P35/04 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  A61P39/02 ,  C07K16/24 ,  C12N1/21 ,  C12N5/10 ,  C12P21/08 ,  G01N33/53 ,  G01N33/543 ,  G01N33/564 ,  G01N33/576 ,  G01N33/68

CPC classification number: C07K16/241 ,  A61K38/00 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/56 ,  C07K2317/565 ,  Y02A50/412 ,  Y10S424/81

Abstract: Human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor alpha(hTNFalpha) are disclosed. These antibodies have high affinity for hTNFalpha (e.g., Kd=10-8 M or less), a slow off rate for hTNFalpha dissociation (e.g., Koff=10-3sec-1 or less) and neutralize hTNFalpha 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 hTNFalpha and for inhibiting hTNFalpha activity, e.g., in a human subject suffering from a disorder in which hTNFalpha 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.

公开(公告)号：NO319955B1

公开(公告)日：2005-10-03

申请号：NO20026202

申请日：2002-12-23

Applicant: BASF AG

Inventor： SALFELD JOCHEN G ,  ALLEN DEBORAH J ,  HOOGENBOOM HENDRICUS R J M ,  KAYMAKCALAN ZEHRA ,  LABKOVSKY BORIS ,  MANKOVICH JOHN A ,  MCGUINNES BRIAN T ,  ROBERTS ANDREW J ,  SAKORAFAS PAUL ,  SCHOENHAUT DAVID ,  VAUGHAN TRISTAN J ,  WHITE MICHAEL ,  WILTON ALISON JANE

IPC: C12N15/09 ,  A61K31/00 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4178 ,  A61K31/505 ,  A61K31/517 ,  A61K31/52 ,  A61K31/529 ,  A61K31/57 ,  A61K31/573 ,  A61K31/675 ,  A61K38/00 ,  A61K38/04 ,  A61K38/16 ,  A61K39/39 ,  A61K39/395 ,  A61P1/00 ,  A61P1/04 ,  A61P1/16 ,  A61P3/10 ,  A61P7/00 ,  A61P7/04 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/16 ,  A61P13/12 ,  A61P17/00 ,  A61P17/02 ,  A61P19/02 ,  A61P19/06 ,  A61P25/00 ,  A61P27/02 ,  A61P29/02 ,  A61P31/00 ,  A61P31/04 ,  A61P31/12 ,  A61P31/18 ,  A61P33/06 ,  A61P35/00 ,  A61P35/04 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  A61P39/02 ,  C07K16/24 ,  C12N1/21 ,  C12N5/10 ,  C12P21/08 ,  G01N33/53 ,  G01N33/543 ,  G01N33/564 ,  G01N33/576 ,  G01N33/68

Abstract: 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.

公开(公告)号：AT239041T

公开(公告)日：2003-05-15

申请号：AT97906572

申请日：1997-02-10

Applicant: BASF AG

Inventor： SALFELD JOCHEN G ,  ALLEN DEBORAH J ,  KAYMAKCALAN ZEHRA ,  LABKOVSKY BORIS ,  MANKOVICH JOHN A ,  MCGUINESS BRIAN T ,  ROBERTS ANDREW J ,  SAKORAFAS PAUL ,  HOOGENBOOM HENDRICUS R J M ,  SCHOENHAUT DAVID ,  VAUGHAN TRISTAN J ,  WHITE MICHAEL ,  WILTON ALISON J

IPC: C12N15/09 ,  A61K31/00 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4178 ,  A61K31/505 ,  A61K31/517 ,  A61K31/52 ,  A61K31/529 ,  A61K31/57 ,  A61K31/573 ,  A61K31/675 ,  A61K38/00 ,  A61K38/04 ,  A61K38/16 ,  A61K39/39 ,  A61K39/395 ,  A61P1/00 ,  A61P1/04 ,  A61P1/16 ,  A61P3/10 ,  A61P7/00 ,  A61P7/04 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/16 ,  A61P13/12 ,  A61P17/00 ,  A61P17/02 ,  A61P19/02 ,  A61P19/06 ,  A61P25/00 ,  A61P27/02 ,  A61P29/02 ,  A61P31/00 ,  A61P31/04 ,  A61P31/12 ,  A61P31/18 ,  A61P33/06 ,  A61P35/00 ,  A61P35/04 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  A61P39/02 ,  C07K16/24 ,  C12N1/21 ,  C12N5/10 ,  C12P21/08 ,  G01N33/53 ,  G01N33/543 ,  G01N33/564 ,  G01N33/576 ,  G01N33/68 ,  C12N15/13 ,  C12N15/64

Abstract: 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.