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：US20180282415A1

公开(公告)日：2018-10-04

申请号：US15765149

申请日：2016-09-27

申请人： Chia-Yang LIN ,  Wei Wei Wu PRIOR ,  Yan QU ,  Changyu WANG ,  Merck Patent GmbH ,  Pfizer Inc.

发明人： Chia-Yang LIN ,  Wei Wei Wu PRIOR ,  Yan QU ,  Changyu WANG

IPC分类号： C07K16/28 ,  A61K39/395 ,  A61K31/439 ,  A61K31/4545 ,  A61P35/00

摘要： The present disclosure describes combination therapies useful for the treatment of cancer. In particular, the invention relates to a combination therapy which comprises a PD-1 axis binding antagonist and an ALK inhibitor for treating cancer.

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：US20120230998A1

公开(公告)日：2012-09-13

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 ,  A61P25/00 ,  A61P19/02 ,  A61P29/00 ,  A61P1/00 ,  A61P9/10 ,  A61P17/00 ,  A61P11/00 ,  A61P25/28 ,  A61K48/00 ,  A61P13/12 ,  C12N5/02 ,  A61P3/10

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：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：US20100077497A1

公开(公告)日：2010-03-25

申请号：US12472877

申请日：2009-05-27

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： A01K67/027 ,  C07K16/18 ,  A61K39/395 ,  C12N5/18 ,  C07H21/04 ,  C12N15/63 ,  A61P31/12 ,  A61P31/04

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：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。