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1. 发明申请

WO2008010101A2 ANTAGONIST ANTIBODY FOR THE TREATMENT OF CANCER 审中-公开
标题翻译：用于治疗癌症的拮抗剂抗体
公开(公告)号：WO2008010101A2
公开(公告)日：2008-01-24
申请号：PCT/IB2007003074
申请日：2007-07-13
申请人： SANOFI AVENTIS , BLANC VERONIQUE , FROMOND CLAUDIA , PARKER FABIENNE , HAN JIAWEN , TAVARES DANIEL , ZHANG CHONGHUI , LI MIN , ZHOU XIAO-MAI , STREULI MICHEL
发明人： BLANC VERONIQUE , FROMOND CLAUDIA , PARKER FABIENNE , HAN JIAWEN , TAVARES DANIEL , ZHANG CHONGHUI , LI MIN , ZHOU XIAO-MAI , STREULI MICHEL
IPC分类号： C07K16/28
CPC分类号： C07K16/28 , A61K39/3955 , A61K45/06 , A61K47/6849 , A61K2039/505 , C07K16/2866 , C07K16/30 , C07K16/40 , C07K2317/24 , C07K2317/73 , C07K2317/76 , C07K2317/92 , G01N33/57492 , G01N2333/705 , G01N2333/91205
摘要： Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to, and inhibit A class of Eph receptors, antagonize the effects of growth factors on the growth and survival of tumor cells, and which have minimal agonistic activity or are preferentially devoid of agonist activity. Said antibodies and fragments thereof may be used in the treatment of tumors that express elevated levels of A class of Eph receptors, such as breast cancer, colon cancer, lung cancer, ovarian carcinoma, synovial sarcoma and pancreatic cancer, and said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of A class of Eph receptors. Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate are disclosed are all embodiments of the invention. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the A class of Eph receptors.
摘要翻译：抗体，人源化抗体，表面抗体，抗体片段，衍生化抗体以及与细胞毒性试剂特异性结合并抑制A类Eph受体的结合物拮抗生长因子对肿瘤细胞生长和存活的影响，并且其具有最小的激动活性或优先没有激动剂活性。所述抗体及其片段可用于治疗表达升高水平的A类Eph受体（例如乳腺癌，结肠癌，肺癌，卵巢癌，滑膜肉瘤和胰腺癌）的肿瘤，并且所述衍生抗体可以是用于诊断和成像表达高水平A类Eph受体的肿瘤。还提供了包含细胞结合剂和细胞毒性剂的细胞毒性缀合物，包含缀合物的治疗组合物，用于抑制细胞生长和治疗疾病的方法以及包含细胞毒性缀合物的试剂盒是所有实施方案的本发明。特别地，细胞结合剂是识别和结合A类Eph受体的单克隆抗体及其表位结合片段。

2. 发明申请

WO2008010101A8 ANTAGONIST ANTIBODY AGAINST EPHA2 FOR THE TREATMENT OF CANCER 审中-公开
标题翻译：拮抗EPHA2抗体治疗癌症的抗体
公开(公告)号：WO2008010101A8
公开(公告)日：2009-03-26
申请号：PCT/IB2007003074
申请日：2007-07-13
申请人： SANOFI AVENTIS , BLANC VERONIQUE , FROMOND CLAUDIA , PARKER FABIENNE , HAN JIAWEN , TAVARES DANIEL , ZHANG CHONGHUI , LI MIN , ZHOU XIAO-MAI , STREULI MICHEL
发明人： BLANC VERONIQUE , FROMOND CLAUDIA , PARKER FABIENNE , HAN JIAWEN , TAVARES DANIEL , ZHANG CHONGHUI , LI MIN , ZHOU XIAO-MAI , STREULI MICHEL
IPC分类号： C07K16/28 , A61K39/395 , A61P35/00 , C12N5/20 , C12N15/13 , C12N15/63 , G01N33/53
CPC分类号： C07K16/28 , A61K39/3955 , A61K45/06 , A61K47/6849 , A61K2039/505 , C07K16/2866 , C07K16/30 , C07K16/40 , C07K2317/24 , C07K2317/73 , C07K2317/76 , C07K2317/92 , G01N33/57492 , G01N2333/705 , G01N2333/91205
摘要： Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to, and inhibit A class of Eph receptors, antagonize the effects of growth factors on the growth and survival of tumor cells, and which have minimal agonistic activity or are preferentially devoid of agonist activity. Said antibodies and fragments thereof may be used in the treatment of tumors that express elevated levels of A class of Eph receptors, such as breast cancer, colon cancer, lung cancer, ovarian carcinoma, synovial sarcoma and pancreatic cancer, and said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of A class of Eph receptors. Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate are disclosed are all embodiments of the invention. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the A class of Eph receptors.
摘要翻译：抗体，人源化抗体，表面重构的抗体，抗体片段，衍生抗体及其与细胞毒性剂的缀合物（其特异性结合并抑制A类Eph受体）拮抗生长因子对肿瘤细胞的生长和存活的影响，并且其具有最小的激动活性或优先没有激动剂活性。所述抗体及其片段可用于治疗表达升高水平的A类Eph受体如乳腺癌，结肠癌，肺癌，卵巢癌，滑膜肉瘤和胰腺癌的肿瘤，并且所述衍生抗体可以是用于诊断和成像表达高水平的A类Eph受体的肿瘤。还提供了包含细胞结合剂和细胞毒性剂的细胞毒性缀合物，包含所述缀合物的治疗性组合物，使用所述缀合物抑制细胞生长和治疗疾病的方法，以及包含所述细胞毒性缀合物的试剂盒，的发明。特别地，细胞结合剂是识别并结合A类Eph受体的单克隆抗体及其表位结合片段。

3. 发明申请

WO2008010101A3 ANTAGONIST ANTIBODY AGAINST EPHA2 FOR THE TREATMENT OF CANCER 审中-公开
标题翻译：用于治疗癌症的抗生素抗体药物EPHA2
公开(公告)号：WO2008010101A3
公开(公告)日：2008-07-17
申请号：PCT/IB2007003074
申请日：2007-07-13
申请人： SANOFI AVENTIS , BLANC VERONIQUE , FROMOND CLAUDIA , PARKER FABIENNE , HAN JIAWEN , TAVARES DANIEL , ZHANG CHONGHUI , LI MIN , ZHOU XIAO-MAI , STREULI MICHEL
发明人： BLANC VERONIQUE , FROMOND CLAUDIA , PARKER FABIENNE , HAN JIAWEN , TAVARES DANIEL , ZHANG CHONGHUI , LI MIN , ZHOU XIAO-MAI , STREULI MICHEL
IPC分类号： C07K16/28 , A61K39/395 , A61P35/00 , C12N5/20 , C12N15/13 , C12N15/63 , G01N33/53
CPC分类号： C07K16/28 , A61K39/3955 , A61K45/06 , A61K47/6849 , A61K2039/505 , C07K16/2866 , C07K16/30 , C07K16/40 , C07K2317/24 , C07K2317/73 , C07K2317/76 , C07K2317/92 , G01N33/57492 , G01N2333/705 , G01N2333/91205
摘要： Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to, and inhibit A class of Eph receptors, antagonize the effects of growth factors on the growth and survival of tumor cells, and which have minimal agonistic activity or are preferentially devoid of agonist activity. Said antibodies and fragments thereof may be used in the treatment of tumors that express elevated levels of A class of Eph receptors, such as breast cancer, colon cancer, lung cancer, ovarian carcinoma, synovial sarcoma and pancreatic cancer, and said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of A class of Eph receptors. Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate are disclosed are all embodiments of the invention. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the A class of Eph receptors.
摘要翻译：抗体，人源化抗体，表面抗体，抗体片段，衍生化抗体以及与细胞毒性试剂特异性结合并抑制A类Eph受体的结合物拮抗生长因子对肿瘤细胞生长和存活的影响，并且其具有最小的激动活性或优先没有激动剂活性。所述抗体及其片段可用于治疗表达升高水平的A类Eph受体（例如乳腺癌，结肠癌，肺癌，卵巢癌，滑膜肉瘤和胰腺癌）的肿瘤，并且所述衍生抗体可以是用于诊断和成像表达高水平A类Eph受体的肿瘤。还提供了包含细胞结合剂和细胞毒性剂的细胞毒性缀合物，包含缀合物的治疗组合物，用于抑制细胞生长和治疗疾病的方法以及包含细胞毒性缀合物的试剂盒是所有实施方案的本发明。特别地，细胞结合剂是识别和结合A类Eph受体的单克隆抗体及其表位结合片段。

4. 发明专利

BRPI0714871A2 未知
公开(公告)号：BRPI0714871A2
公开(公告)日：2013-05-07
申请号：BRPI0714871
申请日：2007-07-13
申请人： SANOFI AVENTIS
发明人： BLANC VERONIQUE , FROMOND CLAUDIA , PARKER FABIENNE , HAN JIAWEN , TAVARES DANIEL , ZHANG CHONGHUI , LI MIN , ZHOU XIAO-MAI , STREULI MICHEL
IPC分类号： C07K16/28 , A61K39/395 , A61P35/00 , C12N5/20 , C12N15/13 , C12N15/63 , G01N33/53
摘要： Antagonistic antibodies that specifically bind to and inhibit Class A Eph receptors are provided. Also provided are cytotoxic conjugates, pharmaceutical compositions and kits comprising these antibodies.

5. 发明专利

ZA200900545B Antagonist antibody against EPHA2 for the treatment of cancer 未知
公开(公告)号：ZA200900545B
公开(公告)日：2010-03-31
申请号：ZA200900545
申请日：2007-07-13
申请人： SANOFI AVENTIS
发明人： BLANC VERONIQUE , FROMOND CLAUDIA , PARKER FABIENNE , HAN JIAWEN , TAVARES DANIEL , ZHANG CHONGHUI , LI MIN , ZHOU XIAO-MAI , STREULI MICHEL
IPC分类号： A61K20100101 , A61P20100101 , C07K20100101 , C12N20100101 , G01N20100101
摘要： Antagonistic antibodies that specifically bind to and inhibit Class A Eph receptors are provided. Also provided are cytotoxic conjugates, pharmaceutical compositions and kits comprising these antibodies.

6. 发明专利

NO20090758A 未知
公开(公告)号：NO20090758A
公开(公告)日：2009-03-17
申请号：NO20090758
申请日：2009-02-17
申请人： SANOFI AVENTIS
发明人： TAVARES DANIEL , BLANC VERONIQUE , FROMOND CLAUDIA , PARKER FABIENNE , HAN JIAWEN , ZHANG CHONGHUI , LI MIN , ZHOU XIAO-MAI , STREULI MICHEL
IPC分类号： C07K16/28 , A61K39/395 , A61P35/00 , C07K16/18 , C12N5/20 , C12N15/13 , C12N15/63 , G01N33/53
CPC分类号： C07K16/28 , A61K39/3955 , A61K45/06 , A61K47/6849 , A61K2039/505 , C07K16/2866 , C07K16/30 , C07K16/40 , C07K2317/24 , C07K2317/73 , C07K2317/76 , C07K2317/92 , G01N33/57492 , G01N2333/705 , G01N2333/91205

7. 发明专利

ECSP099074A ANTICUERPO ANTAGONISTA PARA EL TRATAMIENTO DEL CÁNCER 未知
公开(公告)号：ECSP099074A
公开(公告)日：2009-02-27
申请号：ECSP099074
申请日：2009-01-16
申请人： SANOFI AVENTIS
发明人： TAVARES DANIEL , BLANC VERONIQUE , FROMOND CLAUDIA , PARKER FABIENNE , HAN JIAWEN , ZHANG CHONGHUI , LI MIN , ZHOU XIAO-MAI , STREULI MICHEL
IPC分类号： A61K39/395 , A61P35/00
摘要： Anticuerpos, anticuerpos humanizados, anticuerpos modificados en superficie, fragmentos de anticuerpos, anticuerpos derivatizados, y conjugados de éstos con agentes citotóxicos, que se unen específicamente a, e inhiben la clase A de los receptores Eph, antagonizan los efectos de factores de crecimiento en el crecimiento y supervivencia de células tumorales, y que tienen una actividad agonista mínima o que preferiblemente carecen de actividad agonista. Dichos anticuerpos y fragmentos de éstos pueden utilizarse en el tratamiento de tumores que expresan niveles elevados de la clase A de receptores Eph, tales como cáncer de mama, cáncer de colon, cáncer de pulmón, carcinoma de ovario, sarcoma sinovial y cáncer pancreático, y dichos anticuerpos derivatizados pueden utilizarse en el diagnóstico y en la obtención de imágenes de tumores que expresan niveles elevados de la clase A de receptores Eph. También se proporcionan conjugados citotóxicos que comprenden un agente de unión a células y un agente citotóxico, se describen composiciones terapéuticas que comprenden el conjugado, métodos para utilizar los conjugados en la inhibición del crecimiento celular y en el tratamiento de la enfermedad, y un kit que comprende el conjugado citotóxico, siendo todas realizaciones de la invención. En particular, el agente de unión a células es un anticuerpo monoclonal, y fragmentos de éste que se unen al epítopo, que reconoce y se une a la clase A de receptores Eph.

8. 发明专利

NZ574215A ANTAGONIST ANTIBODY AGAINST EPHA2 FOR THE TREATMENT OF CANCER 未知
公开(公告)号：NZ574215A
公开(公告)日：2012-07-27
申请号：NZ57421507
申请日：2007-07-13
申请人： SANOFI AVENTIS
发明人： BLANC VERONIQUE , FROMOND CLAUDIA , PARKER FABIENNE , HAN JIAWEN , TAVARES DANIEL , ZHANG CHONGHUI , LI MIN , ZHOU XIAO-MAI , STREULI MICHEL
IPC分类号： A61P35/00 , A61K39/395 , C07K16/28 , C12N5/20 , C12N15/13 , C12N15/63 , G01N33/53
摘要： Provided is an antibody or an epitope-binding fragment thereof that specifically binds to an EphA2 receptor and is an antagonist of said receptor. The antibody inhibits EphA2 tyrosine phosphorylation in the presence of ephrinA1. Medicaments containing the antibody can inhibit the migration of cancer cells and can be used to treat various cancers. Further provided are specific antibody sequences and deposited hybridomas producing the antibodies. The antibodies may be conjugated with cytotoxic agents.

9. 发明专利

AR078471A1 COMPUESTOS MAITANSINOIDES Y EL USO DE ESTOS PARA PREPARAR CONJUGADOS CON UN ANTICUERPO LOS CUALES SE UTILIZAN COMO AGENTES ANTICANCERIGENOS Y EL PROCEDIMIENTO DE PREPARACIoN DE ESTOS CONJUGADOS 未知
公开(公告)号：AR078471A1
公开(公告)日：2011-11-09
申请号：ARP100103531
申请日：2010-09-29
申请人： SANOFI AVENTIS
发明人： BOUCHARD HERVE , COMMERCON ALAIN , FROMOND CLAUDIA , PARKER FABIENNE , SASSOON INGRID , MIKOL VINCENT , TAVARES DANIEL
IPC分类号： C07D498/14 , A61K31/5365 , A61P35/00 , C12P21/08
摘要： Compuesto de la formula (1), en donde: ALK es un grupo alquileno C1-6; X1 y X2 son cada uno independientemente uno de los grupos siguientes -CH=CH-, -CO-, -CONR-, -NRCO-, -COO-, -OCO-, -OCONR-, -NRCOO-, -NRCONR'-, -NR-, -S(O)n (n = 0, 1 o 2) o -O-; R y R' son independientemente H o un grupo alquilo C1-6; i es un numero entero de 1 a 40, preferiblemente de 1 a 20, y más preferiblemente de 1 a 10; j es un numero entero que corresponde a 1 cuando X2 es -CH=CH- y 2 cuando X2 no es -CH=CH-; Zb es un enlace sencillo, -O- o -NH- y Rb es H o un grupo alquilo C1-6, cicloalquilo C3-7, arilo, heteroarilo o heterocicloalquilo C3-7; o Zb es un enlace sencillo y Rb es Hal. Su uso como anticancerígeno. Reivindicacion 17: Conjugado segun la reivindicacion 16 que tiene un DAR promedio, medido con un espectrometro UV por encima de 4, más particularmente entre 4 y 10, incluso más particularmente entre 4 y 7, estando determinado el DAR mediante la ecuacion siguiente: DAR = cD / cA con: cD = [(eA280 x A252) - (eA252 x A280)] / [(eD252 x eA280) - (eA252 x eD280)]; cA = [A280 - (cD x eD280)] / eA280; eD252 = 26.159 M-1cm-1; eD280 = 5.180 M-1cm-1; eA280 = 224.000 M-1cm-1; eA252 = 82.880 M-1cm-1; siendo A252 y A280 las absorbancias del conjugado medidas en el espectrometro UV a 252 y 280 hm respectivamente.

10. 发明专利

AR078470A1 ANTICUERPOS QUE SE UNEN ESPECIFICAMENTE AL RECEPTOR EPHA2 未知
公开(公告)号：AR078470A1
公开(公告)日：2011-11-09
申请号：ARP100103530
申请日：2010-09-29
申请人： SANOFI AVENTIS
发明人： SASSOON INGRID , MIKOL VINCENT , BOUCHARD HERVE , COMMERCON ALAIN , PARKER FABIENNE , FROMOND CLAUDIA , TAVARES DANIEL
IPC分类号： C07K16/30 , C07K19/00 , C07K1/02 , A61K39/395 , A61P35/00
摘要： Anticuerpo o fragmentos que se unen al epítopo que se une específicamente a un receptor EphA2. Además se refiere a un conjugado que comprende un agente citotoxico que está unido covalentemente al anticuerpo y a un método para preparar tal conjugado. Composicion farmacéutica, uso del anticuerpo para preparar un medicamento para tratar el cáncer y un kit. Reivindicacion 5: Un conjugado de un anticuerpo o un fragmento que se une al epítopo segun las reivindicaciones 1 - 4, en donde dicho conjugado comprende un agente citotoxico que se elige entre: a) el maitansinoide de formula (1); b) el maitansinoide de formula (2); c) el maitansinoide de formula (3); d) el maitansinoide de formula (4); e) el maitansinoide de formula (5); f) el maitansinoide de formula (6).

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