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    Anti-CTLA-4 antibodies with reduced blocking of binding of CTLA-4 to B7 and uses thereof
    1.
    发明授权
    Anti-CTLA-4 antibodies with reduced blocking of binding of CTLA-4 to B7 and uses thereof 有权
    具有降低的CTLA-4与B7结合的抗CTLA-4抗体及其用途

    公开(公告)号：US08263073B2

    公开(公告)日：2012-09-11

    申请号：US12866149

    申请日：2009-02-04

    申请人： Alan Korman ,  Edward L. Halk ,  Changyu Wang ,  Kent B. Thudium ,  Lan Yang ,  Kristopher Toy

    发明人： Alan Korman ,  Edward L. Halk ,  Changyu Wang ,  Kent B. Thudium ,  Lan Yang ,  Kristopher Toy

    IPC分类号： A61K39/395

    CPC分类号： C07K16/2818 ,  A61K39/3955 ,  A61K2039/55516 ,  C07K2317/52 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  A61K2300/00

    摘要： The present invention provides isolated monoclonal antibodies that bind to CTLA-4 and that are capable of increasing the response of T cells to antigenic stimulation in vivo yet the antibodies do not substantially block the binding of CTLA-4 to B7 ligands (e.g., B7-1 and B7-2) in vitro. Thus, the antibodies of the invention demonstrate that is it possible to separate the immunostimulatory function of anti-CTLA-4 antibodies from their ability to block the binding of B7 ligands. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for increasing the response of T cells to antigenic stimulation using the antibodies of the invention, including methods for treating cancer using the antibodies of the invention.

    摘要翻译： 本发明提供了与CTLA-4结合并且能够增加T细胞对体内抗原刺激的反应的分离的单克隆抗体，但是该抗体基本上不阻断CTLA-4与B7配体的结合（例如，B7- 1和B7-2）。 因此，本发明的抗体证明可以将抗CTLA-4抗体的免疫刺激功能从其阻断B7配体结合的能力分离出来。 还提供了免疫偶联物，双特异性分子和包含本发明抗体的药物组合物。 本发明还提供了使用本发明的抗体增加T细胞对抗原刺激的应答的方法，包括使用本发明的抗体治疗癌症的方法。

    ANTI-CTLA-4 ANTIBODIES WITH REDUCED BLOCKING OF BINDING OF CTLA-4 TO B7 AND USES THEREOF
    2.
    发明申请
    ANTI-CTLA-4 ANTIBODIES WITH REDUCED BLOCKING OF BINDING OF CTLA-4 TO B7 AND USES THEREOF 有权
    抗CTLA-4抗CTLA-4与B7结合阻断的抗体及其用途

    公开(公告)号：US20110081354A1

    公开(公告)日：2011-04-07

    申请号：US12866149

    申请日：2009-02-04

    申请人： Alan Korman ,  Edward L. Halk ,  Changyu Wang ,  Kent B. Thudium ,  Lan Yang ,  Kristopher Toy

    发明人： Alan Korman ,  Edward L. Halk ,  Changyu Wang ,  Kent B. Thudium ,  Lan Yang ,  Kristopher Toy

    IPC分类号： A61K39/395 ,  C07K16/28 ,  A61P35/00

    CPC分类号： C07K16/2818 ,  A61K39/3955 ,  A61K2039/55516 ,  C07K2317/52 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  A61K2300/00

    摘要： The present invention provides isolated monoclonal antibodies that bind to CTLA-4 and that are capable of increasing the response of T cells to antigenic stimulation in vivo yet the antibodies do not substantially block the binding of CTLA-4 to B7 ligands (e.g., B7-1 and B7-2) in vitro. Thus, the antibodies of the invention demonstrate that is it possible to separate the immunostimulatory function of anti-CTLA-4 antibodies from their ability to block the binding of B7 ligands. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for increasing the response of T cells to antigenic stimulation using the antibodies of the invention, including methods for treating cancer using the antibodies of the invention.

    摘要翻译： 本发明提供了与CTLA-4结合并且能够增加T细胞对体内抗原刺激的反应的分离的单克隆抗体，但是该抗体基本上不阻断CTLA-4与B7配体的结合（例如，B7- 1和B7-2）。 因此，本发明的抗体证明可以将抗CTLA-4抗体的免疫刺激功能从其阻断B7配体结合的能力分离出来。 还提供了免疫偶联物，双特异性分子和包含本发明抗体的药物组合物。 本发明还提供了使用本发明的抗体增加T细胞对抗原刺激的应答的方法，包括使用本发明的抗体治疗癌症的方法。

    Human antibodies that bind mesothelin, and uses thereof
    4.
    发明授权
    Human antibodies that bind mesothelin, and uses thereof 有权
    结合间皮素的人抗体及其用途

    公开(公告)号：US08268970B2

    公开(公告)日：2012-09-18

    申请号：US12681215

    申请日：2008-09-29

    申请人： Jonathan A. Terrett ,  Sarah L. Pogue ,  Kristopher Toy ,  Lan Yang ,  Chetana Rao-Naik ,  Bingliang Chen

    发明人： Jonathan A. Terrett ,  Sarah L. Pogue ,  Kristopher Toy ,  Lan Yang ,  Chetana Rao-Naik ,  Bingliang Chen

    IPC分类号： C07K16/00 ,  C12P21/08

    CPC分类号： C07K16/30 ,  A61K39/39558 ,  A61K47/6857 ,  A61K47/6859 ,  A61K47/6863 ,  A61K47/6869 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/41 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/80 ,  C07K2317/92 ,  A61K2300/00

    摘要： The present disclosure provides isolated monoclonal antibodies that specifically bind to mesothelin with high affinity, particularly human monoclonal antibodies. Preferably, the antibodies bind human mesothelin. In certain embodiments, the antibodies are capable of internalizing into mesothelin-expressing cells or are capable of mediating antigen dependent cellular cytotoxicity. The invention further provides anti-mesothelin antibodies that can inhibit the binding of mesothelin to the ovarian cancer antigen CA125. Nucleic acid molecules encoding the antibodies of this disclosure, expression vectors, host cells and methods for expressing the antibodies of this disclosure are also provided. Antibody-partner molecule conjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of this disclosure are also provided. This disclosure also provides methods for detecting mesothelin, as well as methods for treating cancers, such as mesotheliomas, pancreatic cancers and ovarian cancers, using an anti-mesothelin antibody of this disclosure.

    摘要翻译： 本公开提供以高亲和力特别是人单克隆抗体特异性结合间皮素的分离的单克隆抗体。 优选地，所述抗体结合人间皮素。 在某些实施方案中，抗体能够内化成表达间皮素的细胞或能够介导抗原依赖性细胞毒性。 本发明还提供可以抑制间皮素与卵巢癌抗原CA125的结合的抗间皮素抗体。 还提供了编码本公开的抗体的核酸分子，表达载体，宿主细胞和用于表达本公开的抗体的方法。 还提供了抗体 - 配偶体分子缀合物，双特异性分子和包含本公开的抗体的药物组合物。 本公开还提供了用于检测间皮素的方法，以及使用本公开的抗间皮素抗体治疗癌症的方法，例如间皮瘤，胰腺癌和卵巢癌。

    HUMAN ANTIBODIES THAT BIND MESOTHELIN, AND USES THEREOF
    8.
    发明申请
    HUMAN ANTIBODIES THAT BIND MESOTHELIN, AND USES THEREOF 有权
    MESOTHELIN的人体抗体及其用途

    公开(公告)号：US20110262448A1

    公开(公告)日：2011-10-27

    申请号：US12681215

    申请日：2008-09-29

    申请人： Jonathan A. TERRETT ,  Sarah L. Pogue ,  Kristopher Toy ,  Lan Yang ,  Chetana Rao-Naik ,  Bingliang Chen

    发明人： Jonathan A. TERRETT ,  Sarah L. Pogue ,  Kristopher Toy ,  Lan Yang ,  Chetana Rao-Naik ,  Bingliang Chen

    IPC分类号： A61K39/395 ,  A61P35/00 ,  A61K39/44 ,  C07K16/18

    CPC分类号： C07K16/30 ,  A61K39/39558 ,  A61K47/6857 ,  A61K47/6859 ,  A61K47/6863 ,  A61K47/6869 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/41 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/80 ,  C07K2317/92 ,  A61K2300/00

    摘要： The present disclosure provides isolated monoclonal antibodies that specifically bind to mesothelin with high affinity, particularly human monoclonal antibodies. Preferably, the antibodies bind human mesothelin. In certain embodiments, the antibodies are capable of internalizing into mesothelin-expressing cells or are capable of mediating antigen dependent cellular cytotoxicity. The invention further provides anti-mesothelin antibodies that can inhibit the binding of mesothelin to the ovarian cancer antigen CA125. Nucleic acid molecules encoding the antibodies of this disclosure, expression vectors, host cells and methods for expressing the antibodies of this disclosure are also provided. Antibody-partner molecule conjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of this disclosure are also provided. This disclosure also provides methods for detecting mesothelin, as well as methods for treating cancers, such as mesotheliomas, pancreatic cancers and ovarian cancers, using an anti-mesothelin antibody of this disclosure.

    摘要翻译： 本公开提供以高亲和力特别是人单克隆抗体特异性结合间皮素的分离的单克隆抗体。 优选地，所述抗体结合人间皮素。 在某些实施方案中，抗体能够内化成表达间皮素的细胞或能够介导抗原依赖性细胞毒性。 本发明还提供可以抑制间皮素与卵巢癌抗原CA125的结合的抗间皮素抗体。 还提供了编码本公开的抗体的核酸分子，表达载体，宿主细胞和用于表达本公开的抗体的方法。 还提供了抗体 - 配偶体分子缀合物，双特异性分子和包含本公开的抗体的药物组合物。 本公开还提供了使用本公开的抗间皮素抗体检测间皮素的方法以及用于治疗癌症的方法，诸如间皮瘤，胰腺癌和卵巢癌。

    Human antibodies that bind mesothelin, and uses thereof
    10.
    发明授权
    Human antibodies that bind mesothelin, and uses thereof 有权
    结合间皮素的人抗体及其用途

    公开(公告)号：US08399623B2

    公开(公告)日：2013-03-19

    申请号：US13587500

    申请日：2012-08-16

    申请人： Jonathan A. Terrett ,  Sarah L. Pogue ,  Kristopher Toy ,  Lan Yang ,  Chetana Rao-Naik ,  Bingliang Chen

    发明人： Jonathan A. Terrett ,  Sarah L. Pogue ,  Kristopher Toy ,  Lan Yang ,  Chetana Rao-Naik ,  Bingliang Chen

    IPC分类号： C07K16/00 ,  C12P21/08

    CPC分类号： C07K16/30 ,  A61K39/39558 ,  A61K47/6857 ,  A61K47/6859 ,  A61K47/6863 ,  A61K47/6869 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/41 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/80 ,  C07K2317/92 ,  A61K2300/00

    摘要： The present disclosure provides isolated monoclonal antibodies that specifically bind to mesothelin with high affinity, particularly human monoclonal antibodies. Preferably, the antibodies bind human mesothelin. In certain embodiments, the antibodies are capable of internalizing into mesothelin-expressing cells or are capable of mediating antigen dependent cellular cytotoxicity. The invention further provides anti-mesothelin antibodies that can inhibit the binding of mesothelin to the ovarian cancer antigen CA125. Nucleic acid molecules encoding the antibodies of this disclosure, expression vectors, host cells and methods for expressing the antibodies of this disclosure are also provided. Antibody-partner molecule conjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of this disclosure are also provided. This disclosure also provides methods for detecting mesothelin, as well as methods for treating cancers, such as mesotheliomas, pancreatic cancers and ovarian cancers, using an anti-mesothelin antibody of this disclosure.

    摘要翻译： 本公开提供以高亲和力特别是人单克隆抗体特异性结合间皮素的分离的单克隆抗体。 优选地，所述抗体结合人间皮素。 在某些实施方案中，抗体能够内化成表达间皮素的细胞或能够介导抗原依赖性细胞毒性。 本发明还提供可以抑制间皮素与卵巢癌抗原CA125的结合的抗间皮素抗体。 还提供了编码本公开的抗体的核酸分子，表达载体，宿主细胞和用于表达本公开的抗体的方法。 还提供了抗体 - 配偶体分子缀合物，双特异性分子和包含本公开的抗体的药物组合物。 本公开还提供了使用本公开的抗间皮素抗体检测间皮素的方法以及用于治疗癌症的方法，诸如间皮瘤，胰腺癌和卵巢癌。