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。

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。

公开(公告)号：US08945546B2

公开(公告)日：2015-02-03

申请号：US13478786

申请日：2012-05-23

申请人： Shrikant Deshpande ,  Haichun Huang ,  Mohan Srinivasan ,  Josephine M. Cardarelli ,  Changyu Wang ,  David Passmore ,  Vangipuram Rangan ,  Thomas E. Lane ,  Hans S. Keirstead ,  Michael T. Liu

发明人： Shrikant Deshpande ,  Haichun Huang ,  Mohan Srinivasan ,  Josephine M. Cardarelli ,  Changyu Wang ,  David Passmore ,  Vangipuram Rangan ,  Thomas E. Lane ,  Hans S. Keirstead ,  Michael T. Liu

IPC分类号： A61K39/395 ,  A61K39/40 ,  C07K14/52 ,  C07K16/24 ,  A61K39/00

CPC分类号： C07K16/24 ,  A61K2039/505 ,  C07K14/522 ,  C07K2317/21 ,  C07K2317/33 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/76 ,  C07K2317/92

摘要： The present invention provides isolated monoclonal antibodies, particularly human antibodies, that bind to IP-10 with high affinity, inhibit the binding of IP-10 to its receptor, inhibit IP-10-induced calcium flux and inhibit IP-10-induced cell migration. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting IP-10 activity using the antibodies of the invention, including methods for treating various inflammatory and autoimmune diseases.

摘要翻译： 本发明提供以高亲和力结合IP-10的分离的单克隆抗体，特别是人抗体，抑制IP-10与其受体的结合，抑制IP-10诱导的钙通量并抑制IP-10诱导的细胞迁移 。 还提供了编码本发明抗体的核酸分子，表达载体，宿主细胞和用于表达本发明的抗体的方法。 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来抑制IP-10活性的方法，包括治疗各种炎性和自身免疫性疾病的方法。

公开(公告)号：US08779105B2

公开(公告)日：2014-07-15

申请号：US13210137

申请日：2011-08-15

申请人： Alan J. Korman ,  Mohan Srinivasan ,  Changyu Wang ,  Mark J. Selby ,  Bing Chen ,  Josephine M. Cardarelli ,  Haichun Huang

发明人： Alan J. Korman ,  Mohan Srinivasan ,  Changyu Wang ,  Mark J. Selby ,  Bing Chen ,  Josephine M. Cardarelli ,  Haichun Huang

IPC分类号： C07K16/28 ,  C07K16/18 ,  A61K39/00

CPC分类号： A61K39/39558 ,  A61K39/00 ,  A61K39/3955 ,  A61K47/6849 ,  A61K51/10 ,  A61K2039/505 ,  A61K2039/507 ,  C07K16/18 ,  C07K16/28 ,  C07K16/2803 ,  C07K16/2818 ,  C07K16/468 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/33 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/74 ,  C07K2317/75 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2317/94

摘要： The present invention provides isolated monoclonal antibodies, particularly human monoclonal antibodies, that specifically bind to PD-1 with high affinity. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for detecting PD-1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-1 antibodies. The present invention further provides methods for using a combination immunotherapy, such as the combination of anti-CTLA-4 and anti-PD-1 antibodies, to treat hyperproliferative disease, such as cancer. The invention also provides methods for altering adverse events related to treatment with such antibodies individually.

摘要翻译： 本发明提供以高亲和力特异性结合PD-1的分离的单克隆抗体，特别是人单克隆抗体。 还提供了编码本发明抗体的核酸分子，表达载体，宿主细胞和用于表达本发明的抗体的方法。 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。 本发明还提供用于检测PD-1的方法，以及使用抗PD-1抗体治疗各种疾病（包括癌症和感染性疾病）的方法。 本发明还提供了使用组合免疫治疗如抗CTLA-4和抗-PD-1抗体的组合来治疗过度增殖性疾病如癌症的方法。 本发明还提供用于改变与用这种抗体单独治疗相关的不良事件的方法。

公开(公告)号：US20130133091A1

公开(公告)日：2013-05-23

申请号：US13210137

申请日：2011-08-15

申请人： Alan J. Korman ,  Mohan Srinivasan ,  Changyu Wang ,  Mark J. Sellby ,  Bing Chen ,  Josephine M. Cardarelli ,  Haichun Huang

发明人： Alan J. Korman ,  Mohan Srinivasan ,  Changyu Wang ,  Mark J. Sellby ,  Bing Chen ,  Josephine M. Cardarelli ,  Haichun Huang

IPC分类号： C07K16/18

CPC分类号： A61K39/39558 ,  A61K39/00 ,  A61K39/3955 ,  A61K47/6849 ,  A61K51/10 ,  A61K2039/505 ,  A61K2039/507 ,  C07K16/18 ,  C07K16/28 ,  C07K16/2803 ,  C07K16/2818 ,  C07K16/468 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/33 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/74 ,  C07K2317/75 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2317/94

摘要： The present invention provides isolated monoclonal antibodies, particularly human monoclonal antibodies, that specifically bind to PD-1 with high affinity. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for detecting PD-1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-1 antibodies. The present invention further provides methods for using a combination immunotherapy, such as the combination of anti-CTLA-4 and anti-PD-1 antibodies, to treat hyperproliferative disease, such as cancer. The invention also provides methods for altering adverse events related to treatment with such antibodies individually.

摘要翻译： 本发明提供以高亲和力特异性结合PD-1的分离的单克隆抗体，特别是人单克隆抗体。 还提供了编码本发明抗体的核酸分子，表达载体，宿主细胞和用于表达本发明的抗体的方法。 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。 本发明还提供用于检测PD-1的方法，以及使用抗PD-1抗体治疗各种疾病（包括癌症和感染性疾病）的方法。 本发明还提供了使用组合免疫治疗如抗CTLA-4和抗-PD-1抗体的组合来治疗过度增殖性疾病如癌症的方法。 本发明还提供用于改变与用这种抗体单独治疗相关的不良事件的方法。

公开(公告)号：US08383796B2

公开(公告)日：2013-02-26

申请号：US13091936

申请日：2011-04-21

申请人： Alan J. Korman ,  Mark J. Selby ,  Changyu Wang ,  Mohan Srinivasan ,  David B. Passmore ,  Haichun Huang ,  Haibin Chen

发明人： Alan J. Korman ,  Mark J. Selby ,  Changyu Wang ,  Mohan Srinivasan ,  David B. Passmore ,  Haichun Huang ,  Haibin Chen

IPC分类号： C07H21/04

CPC分类号： C07K16/2827 ,  A61K45/06 ,  A61K47/6817 ,  A61K47/6825 ,  A61K47/6849 ,  A61K2039/505 ,  C07K16/28 ,  C07K16/2803 ,  C07K16/2818 ,  C07K2317/21 ,  C07K2317/41 ,  C07K2317/56 ,  C07K2317/567 ,  C07K2317/732 ,  C07K2317/74 ,  C07K2317/75 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92 ,  Y02A50/386 ,  Y02A50/403 ,  Y02A50/407 ,  Y02A50/41 ,  Y02A50/412 ,  Y02A50/466

摘要： The present disclosure provides isolated monoclonal antibodies, particularly human monoclonal antibodies that specifically bind to PD-L1 with high affinity. 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. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The disclosure also provides methods for detecting PD-L1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-L1 antibodies.

摘要翻译： 本公开提供分离的单克隆抗体，特别是以高亲和力特异性结合PD-L1的人单克隆抗体。 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。 本公开还提供了使用抗PD-L1抗体检测PD-L1的方法以及用于治疗各种疾病（包括癌症和感染性疾病）的方法。

公开(公告)号：US20110209230A1

公开(公告)日：2011-08-25

申请号：US13091936

申请日：2011-04-21

申请人： Alan J. Korman ,  Mark J. Selby ,  Changyu Wang ,  Mohan Srinivasan ,  David B. Passmore ,  Haichun Huang ,  Haibin Chen

发明人： Alan J. Korman ,  Mark J. Selby ,  Changyu Wang ,  Mohan Srinivasan ,  David B. Passmore ,  Haichun Huang ,  Haibin Chen

IPC分类号： A01K67/027 ,  C07H21/04 ,  C12N15/63 ,  C12N5/10 ,  C12P21/08

CPC分类号： C07K16/2827 ,  A61K45/06 ,  A61K47/6817 ,  A61K47/6825 ,  A61K47/6849 ,  A61K2039/505 ,  C07K16/28 ,  C07K16/2803 ,  C07K16/2818 ,  C07K2317/21 ,  C07K2317/41 ,  C07K2317/56 ,  C07K2317/567 ,  C07K2317/732 ,  C07K2317/74 ,  C07K2317/75 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92 ,  Y02A50/386 ,  Y02A50/403 ,  Y02A50/407 ,  Y02A50/41 ,  Y02A50/412 ,  Y02A50/466

摘要： The present disclosure provides isolated monoclonal antibodies, particularly human monoclonal antibodies that specifically bind to PD-L1 with high affinity. 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. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The disclosure also provides methods for detecting PD-L1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-L1 antibodies.

摘要翻译： 本公开提供分离的单克隆抗体，特别是以高亲和力特异性结合PD-L1的人单克隆抗体。 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。 本公开还提供了使用抗PD-L1抗体检测PD-L1的方法以及用于治疗各种疾病（包括癌症和感染性疾病）的方法。

公开(公告)号：US07943743B2

公开(公告)日：2011-05-17

申请号：US11917727

申请日：2006-06-30

申请人： Alan J. Korman ,  Mark J. Selby ,  Changyu Wang ,  Mohan Srinivasan ,  David B. Passmore ,  Haichun Huang ,  Haibin Chen

发明人： Alan J. Korman ,  Mark J. Selby ,  Changyu Wang ,  Mohan Srinivasan ,  David B. Passmore ,  Haichun Huang ,  Haibin Chen

IPC分类号： C07K16/00

CPC分类号： C07K16/2827 ,  A61K45/06 ,  A61K47/6817 ,  A61K47/6825 ,  A61K47/6849 ,  A61K2039/505 ,  C07K16/28 ,  C07K16/2803 ,  C07K16/2818 ,  C07K2317/21 ,  C07K2317/41 ,  C07K2317/56 ,  C07K2317/567 ,  C07K2317/732 ,  C07K2317/74 ,  C07K2317/75 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92 ,  Y02A50/386 ,  Y02A50/403 ,  Y02A50/407 ,  Y02A50/41 ,  Y02A50/412 ,  Y02A50/466

摘要： The present disclosure provides isolated monoclonal antibodies, particularly human monoclonal antibodies that specifically bind to PD-L1 with high affinity. 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. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The disclosure also provides methods for detecting PD-L1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-L1 antibodies.

摘要翻译： 本公开提供分离的单克隆抗体，特别是以高亲和力特异性结合PD-L1的人单克隆抗体。 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。 本公开还提供了使用抗PD-L1抗体检测PD-L1的方法以及用于治疗各种疾病（包括癌症和感染性疾病）的方法。

公开(公告)号：US20090217401A1

公开(公告)日：2009-08-27

申请号：US11913217

申请日：2006-05-02

申请人： Alan J. Korman ,  Mohan Srinivasan ,  Changyu Wang ,  Mark J. Selby ,  Bing Chen ,  Josephine M. Cardarelli

发明人： Alan J. Korman ,  Mohan Srinivasan ,  Changyu Wang ,  Mark J. Selby ,  Bing Chen ,  Josephine M. Cardarelli

IPC分类号： A01K67/027 ,  A61K39/395 ,  C07H21/00 ,  C12N15/74 ,  C12N5/10 ,  C12N5/16 ,  C07K16/18 ,  A61P35/00

CPC分类号： A61K39/39558 ,  A61K39/00 ,  A61K39/3955 ,  A61K47/6849 ,  A61K51/10 ,  A61K2039/505 ,  A61K2039/507 ,  C07K16/18 ,  C07K16/28 ,  C07K16/2803 ,  C07K16/2818 ,  C07K16/468 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/33 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/74 ,  C07K2317/75 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2317/94

摘要： The present invention provides isolated monoclonal antibodies, particularly human monoclonal antibodies, that specifically bind to PD-1 with high affinity. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for detecting PD-1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-1 antibodies. The present invention further provides methods for using a combination immunotherapy, such as the combination of anti-CTLA-4 and anti-PD-1 antibodies, to treat hyperproliferative disease, such as cancer. The invention also provides methods for altering adverse events related to treatment with such antibodies individually.

摘要翻译： 本发明提供以高亲和力特异性结合PD-1的分离的单克隆抗体，特别是人单克隆抗体。 还提供了编码本发明抗体的核酸分子，表达载体，宿主细胞和用于表达本发明的抗体的方法。 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。 本发明还提供用于检测PD-1的方法，以及使用抗PD-1抗体治疗各种疾病（包括癌症和感染性疾病）的方法。 本发明还提供了使用组合免疫治疗如抗CTLA-4和抗-PD-1抗体的组合来治疗过度增殖性疾病如癌症的方法。 本发明还提供用于改变与用这种抗体单独治疗相关的不良事件的方法。

公开(公告)号：US20110091472A1

公开(公告)日：2011-04-21

申请号：US12979081

申请日：2010-12-27

申请人： Keting Chu ,  Changyu Wang

发明人： Keting Chu ,  Changyu Wang

IPC分类号： A61K39/395 ,  A61P17/06

CPC分类号： C07K16/2878 ,  A61K39/395 ,  A61K2039/505 ,  C07K16/2875 ,  C07K2317/24 ,  A61K2300/00

摘要： CD40 antagonists are used to prepare compositions, including pharmaceutical compositions, for treating autoimmune and neoplastic diseases in a mammal. The CD40 antagonist compositions are useful for reversing or substantially diminishing such autoimmune diseases as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and psoriasis.

摘要翻译： CD40拮抗剂用于制备用于治疗哺乳动物自身免疫性和肿瘤性疾病的组合物，包括药物组合物。 CD40拮抗剂组合物可用于逆转或基本上减少诸如系统性红斑狼疮，类风湿性关节炎，多发性硬化和牛皮癣等自身免疫性疾病。