公开(公告)号：US08552156B2

公开(公告)日：2013-10-08

申请号：US13158622

申请日：2011-06-13

申请人： Shin-ichiro Takayanagi ,  Hitomi Tomura ,  Tomonori Tawara ,  Yoshimasa Inagaki ,  Tsuguo Kubota ,  Koichi Akashi ,  Yoshikane Kikushige

发明人： Shin-ichiro Takayanagi ,  Hitomi Tomura ,  Tomonori Tawara ,  Yoshimasa Inagaki ,  Tsuguo Kubota ,  Koichi Akashi ,  Yoshikane Kikushige

IPC分类号： C07K16/00 ,  A61K39/395

CPC分类号： C07K16/2803 ,  C07K16/2818 ,  C07K2317/14 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/33 ,  C07K2317/34 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/732 ,  C07K2317/92 ,  G01N33/56972

摘要： The present invention provides an anti-human TIM-3 antibody having high ADCC activity or antibody fragment thereof by screening a monoclonal antibody or antibody fragment thereof which binds to the amino acid sequence of the extracellular region of TIM-3 or its three-dimensional structure and exhibits ADCC activity; a hybridoma which produces the antibody; a DNA encoding the antibody; a vector comprising the DNA; a transformant which is obtainable by introducing the vector; a method for producing the antibody or the antibody fragment thereof which comprises using the hybridoma or the transformant; a therapeutic agent and a diagnostic agent comprising the antibody or the antibody fragment thereof as an active ingredient.

摘要翻译： 本发明通过筛选结合TIM-3的胞外区的氨基酸序列的单克隆抗体或其抗体片段或其三维结构，提供具有高ADCC活性的抗人TIM-3抗体或其抗体片段 并展示ADCC活动; 产生抗体的杂交瘤; 编码抗体的DNA; 包含DNA的载体; 通过引入载体可获得的转化体; 包括使用该杂交瘤或转化体的抗体或其抗体片段的制备方法; 包含抗体或其抗体片段的治疗剂和诊断剂作为活性成分。

公开(公告)号：US08647623B2

公开(公告)日：2014-02-11

申请号：US13263434

申请日：2010-04-09

申请人： Shinichiro Takayanagi ,  Yoshimasa Inagaki ,  Koichi Akashi ,  Yoshikane Kikushige

发明人： Shinichiro Takayanagi ,  Yoshimasa Inagaki ,  Koichi Akashi ,  Yoshikane Kikushige

IPC分类号： A61K39/395

CPC分类号： G01N33/57426 ,  A61K2039/505 ,  C07K16/2803 ,  C07K16/3061 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  G01N33/57407 ,  G01N2333/70503

摘要： Disclosed is a therapeutic method comprising administering a TIM-3 antibody to a subject who is suspected to be suffering from blood tumor and in whom TIM-3 has been expressed in a Lin(−)CD34(+)CD38(−) cell fraction of bone marrow or peripheral blood or a subject who has been received any treatment for blood tumor. Also disclosed is a composition for preventing or treating blood tumor, which comprises a TIM-3 antibody as an active ingredient. Conceived diseases include those diseases which can be treated through the binding or targeting of the TIM-3 antibody to blood tumor cells (AML cells, CML cells, MDS cells, ALL cells, CLL cells, multiple myeloma cells, etc.), helper T cell (e.g., Th1 cells, Th17 cells), and antigen-presenting cells (e.g., dendritic cells, monocytes, macrophages, and cells resembling to the aforementioned cells (hepatic stellate cells, osteoclasts, microglial cells, intraepidermal macrophages, dust cells (alveolar macrophages), etc)), all of which are capable of expressing TIM-3. The diseases for which the therapeutic use is to be examined include blood diseases in which the expression of TIM-3 is observed in bone marrow or peripheral blood, particularly blood tumor.

摘要翻译： 公开了一种治疗方法，其包括对怀疑患有血液肿瘤的受试者施用TIM-3抗体，并且在其中已经表达TIM-3的Lin（ - ）CD34（+）CD38（ - ）细胞级分中 骨髓或外周血或受到血肿治疗的受试者。 还公开了用于预防或治疗血液肿瘤的组合物，其包含TIM-3抗体作为活性成分。 想象中的疾病包括可以通过TIM-3抗体对血液肿瘤细胞（AML细胞，CML细胞，MDS细胞，ALL细胞，CLL细胞，多发性骨髓瘤细胞等）的结合或靶向治疗的那些疾病，辅助T 细胞（例如，Th1细胞，Th17细胞）和抗原呈递细胞（例如，树突状细胞，单核细胞，巨噬细胞和类似于上述细胞的细胞（肝星状细胞，破骨细胞，小神经胶质细胞，表皮内巨噬细胞，尘埃细胞（肺泡 巨噬细胞）等）），所有这些都能表达TIM-3。 要检查治疗用途的疾病包括在骨髓或外周血，特别是血肿瘤中观察到TIM-3的表达的血液疾病。

公开(公告)号：US20120100131A1

公开(公告)日：2012-04-26

申请号：US13263434

申请日：2010-04-09

申请人： Shinichiro Takayanagi ,  Yoshimasa Inagaki ,  Koichi Akashi ,  Yoshikane Kikushige

发明人： Shinichiro Takayanagi ,  Yoshimasa Inagaki ,  Koichi Akashi ,  Yoshikane Kikushige

IPC分类号： A61K39/395 ,  A61P35/00

CPC分类号： G01N33/57426 ,  A61K2039/505 ,  C07K16/2803 ,  C07K16/3061 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  G01N33/57407 ,  G01N2333/70503

摘要： Disclosed is a therapeutic method comprising administering a TIM-3 antibody to a subject who is suspected to be suffering from blood tumor and in whom TIM-3 has been expressed in a Lin(−)CD34(+)CD38(−) cell fraction of bone marrow or peripheral blood or a subject who has been received any treatment for blood tumor. Also disclosed is a composition for preventing or treating blood tumor, which comprises a TIM-3 antibody as an active ingredient. Conceived diseases include those diseases which can be treated through the binding or targeting of the TIM-3 antibody to blood tumor cells (AML cells, CML cells, MDS cells, ALL cells, CLL cells, multiple myeloma cells, etc.), helper T cell (e.g., Th1 cells, Th17 cells), and antigen-presenting cells (e.g., dendritic cells, monocytes, macrophages, and cells resembling to the aforementioned cells (hepatic stellate cells, osteoclasts, microglial cells, intraepidermal macrophages, dust cells (alveolar macrophages), etc)), all of which are capable of expressing TIM-3. The diseases for which the therapeutic use is to be examined include blood diseases in which the expression of TIM-3 is observed in bone marrow or peripheral blood, particularly blood tumor.

摘要翻译： 公开了一种治疗方法，其包括对怀疑患有血液肿瘤的受试者施用TIM-3抗体，并且在其中已经表达TIM-3的Lin（ - ）CD34（+）CD38（ - ）细胞级分中 骨髓或外周血或受到血肿治疗的受试者。 还公开了用于预防或治疗血液肿瘤的组合物，其包含TIM-3抗体作为活性成分。 想象中的疾病包括可以通过TIM-3抗体对血液肿瘤细胞（AML细胞，CML细胞，MDS细胞，ALL细胞，CLL细胞，多发性骨髓瘤细胞等）的结合或靶向治疗的那些疾病，辅助T 细胞（例如，Th1细胞，Th17细胞）和抗原呈递细胞（例如，树突状细胞，单核细胞，巨噬细胞和类似于上述细胞的细胞（肝星状细胞，破骨细胞，小神经胶质细胞，表皮内巨噬细胞，尘埃细胞（肺泡 巨噬细胞）等）），所有这些都能表达TIM-3。 要检查治疗用途的疾病包括在骨髓或外周血，特别是血肿瘤中观察到TIM-3的表达的血液疾病。