公开(公告)号：US08632996B2

公开(公告)日：2014-01-21

申请号：US13492465

申请日：2012-06-08

申请人： Kenya Shitara ,  Nobuo Hanai ,  Emi Shoji ,  Mikiko Sakurada ,  Akiko Furuya ,  Kazuyasu Nakamura ,  Rinpei Niwa ,  Kenji Shibata ,  Motoo Yamasaki

发明人： Kenya Shitara ,  Nobuo Hanai ,  Emi Shoji ,  Mikiko Sakurada ,  Akiko Furuya ,  Kazuyasu Nakamura ,  Rinpei Niwa ,  Kenji Shibata ,  Motoo Yamasaki

IPC分类号： C12P21/00

CPC分类号： G01N33/543 ,  A61K2039/505 ,  C07K16/2866 ,  C07K2317/24 ,  C07K2317/565 ,  C07K2317/732 ,  C07K2319/00 ,  G01N2333/78

摘要： A recombinant antibody or the antibody fragment thereof which specifically reacts with an extracellular domain of human CCR4; a DNA which encodes the recombinant antibody or the antibody fragment thereof; a method for producing the recombinant antibody or the antibody fragment thereof; a method for immunologically detecting CCR4, a method for immunologically detecting a cell which expressed CCR4 on the cell surface, a method for depleting a cell which expresses CCR4 on the cell surface, and a method for inhibiting production of Th2 cytokine, which comprise using the recombinant antibody according or antibody fragment thereof; a therapeutic or diagnostic agent for Th2-mediated immune diseases; and a therapeutic or diagnostic agent for a blood cancer.

摘要翻译： 与人CCR4的细胞外结构域特异性反应的重组抗体或其抗体片段; 编码重组抗体或其抗体片段的DNA; 制备重组抗体或其抗体片段的方法; 用于免疫学检测CCR4的方法，用于免疫检测在细胞表面上表达CCR4的细胞的方法，用于在细胞表面上表达CCR4的细胞消耗的方法，以及抑制Th2细胞因子产生的方法，其包括使用 重组抗体或其抗体片段; Th2介导的免疫疾病的治疗或诊断剂; 和用于血液癌的治疗或诊断剂。

公开(公告)号：US08481039B2

公开(公告)日：2013-07-09

申请号：US13365769

申请日：2012-02-03

申请人： Eisuke Mekada ,  Ryo Iwamoto ,  Shingo Miyamoto ,  Kenya Shitara ,  Akiko Furuya ,  Kazuyasu Nakamura ,  Kumiko Takahashi ,  Hiroshi Ando ,  Kazuhiro Masuda ,  Yuka Sasaki

发明人： Eisuke Mekada ,  Ryo Iwamoto ,  Shingo Miyamoto ,  Kenya Shitara ,  Akiko Furuya ,  Kazuyasu Nakamura ,  Kumiko Takahashi ,  Hiroshi Ando ,  Kazuhiro Masuda ,  Yuka Sasaki

IPC分类号： A61K39/395 ,  A61K39/00 ,  C12P21/08 ,  C07K1/00

CPC分类号： A61K39/39558 ,  A61K2039/505 ,  C07K16/22 ,  C07K16/30 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/76

摘要： Medicaments for treating diseases related to HB-EGF escalation are in demand. The present invention provides a monoclonal antibody or an antibody fragment thereof which binds to a cell membrane-bound HB-EGF, a membrane type HB-EGF and a secretory HB-EGF.

摘要翻译： 需要用于治疗与HB-EGF升高有关的疾病的药物。 本发明提供了结合细胞膜结合的HB-EGF，膜型HB-EGF和分泌型HB-EGF的单克隆抗体或其抗体片段。

公开(公告)号：US08313913B2

公开(公告)日：2012-11-20

申请号：US12550160

申请日：2009-08-28

申请人： Kazuyasu Nakamura ,  Kenya Shitara

发明人： Kazuyasu Nakamura ,  Kenya Shitara

IPC分类号： G01N31/00 ,  C07K16/00

CPC分类号： C12P21/02 ,  A61K39/395 ,  C07K16/22 ,  C07K16/283 ,  C07K16/2866 ,  C07K16/3084 ,  C07K2317/24 ,  C07K2317/41 ,  C07K2317/732 ,  C07K2319/30

摘要： A method for enhancing a binding activity of an antibody composition to Fcγ receptor IIIa, which comprises modifying a complex N-glycoside-linked sugar chain which is bound to the Fc region of an antibody molecule; a method for enhancing an antibody-dependent cell-mediated cytotoxic activity of an antibody composition; a process for producing an antibody composition having an enhanced binding activity to Fcγ receptor IIIa; a method for detecting the ratio of a sugar chain in which fucose is not bound to N-acetylglucosamine in the reducing end in the sugar chain among total complex N-glycoside-linked sugar chains bound to the Fc region in an antibody composition; an Fc fusion protein composition produced by using a cell resistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α-bond in a complex N-glycoside-linked sugar chain; and a process for producing the same.

摘要翻译： 一种增强抗体组合物与Fcγ受体IIIa的结合活性的方法，其包括修饰与抗体分子的Fc区结合的复合N-糖苷连接的糖链; 用于增强抗体依赖性细胞介导的抗体组合物的细胞毒活性的方法; 制备对Fcγ受体IIIa具有增强的结合活性的抗体组合物的方法; 在抗体组合物中与Fc区结合的总复合N-糖苷连接的糖链中，检测糖链与还原末端中的岩藻糖不与N-乙酰葡糖胺结合的糖链的比例的方法; 通过使用对凝集素有抗性的细胞产生的Fc融合蛋白质组合物，所述细胞通过复合N-糖苷中的α-键识别糖链的1-位与还原末端的N-乙酰葡糖胺的6-位结合的糖链 链糖链 及其制造方法。

公开(公告)号：US08197814B2

公开(公告)日：2012-06-12

申请号：US12684651

申请日：2010-01-08

申请人： Kenya Shitara ,  Nobuo Hanai ,  Emi Shoji ,  Mikiko Sakurada ,  Akiko Furuya ,  Kazuyasu Nakamura ,  Rinpei Niwa ,  Kenji Shibata ,  Motoo Yamasaki

发明人： Kenya Shitara ,  Nobuo Hanai ,  Emi Shoji ,  Mikiko Sakurada ,  Akiko Furuya ,  Kazuyasu Nakamura ,  Rinpei Niwa ,  Kenji Shibata ,  Motoo Yamasaki

IPC分类号： A61K39/395

CPC分类号： G01N33/543 ,  A61K2039/505 ,  C07K16/2866 ,  C07K2317/24 ,  C07K2317/565 ,  C07K2317/732 ,  C07K2319/00 ,  G01N2333/78

摘要： A recombinant antibody or the antibody fragment thereof which specifically reacts with an extracellular domain of human CCR4; a DNA which encodes the recombinant antibody or the antibody fragment thereof; a method for producing the recombinant antibody or the antibody fragment thereof; a method for immunologically detecting CCR4, a method for immunologically detecting a cell which expressed CCR4 on the cell surface, a method for depleting a cell which expresses CCR4 on the cell surface, and a method for inhibiting production of Th2 cytokine, which comprise using the recombinant antibody according or antibody fragment thereof; a therapeutic or diagnostic agent for Th2-mediated immune diseases; and a therapeutic or diagnostic agent for a blood cancer.

摘要翻译： 与人CCR4的细胞外结构域特异性反应的重组抗体或其抗体片段; 编码重组抗体或其抗体片段的DNA; 制备重组抗体或其抗体片段的方法; 用于免疫学检测CCR4的方法，用于免疫检测在细胞表面上表达CCR4的细胞的方法，用于在细胞表面上表达CCR4的细胞消耗的方法，以及抑制Th2细胞因子产生的方法，其包括使用 重组抗体或其抗体片段; Th2介导的免疫疾病的治疗或诊断剂; 和用于血液癌的治疗或诊断剂。

公开(公告)号：US07615214B2

公开(公告)日：2009-11-10

申请号：US11250411

申请日：2005-10-17

申请人： Kenya Shitara ,  Mikito Ito ,  Nobuo Hanai ,  Yoko Kawada ,  Kazuyasu Nakamura ,  Masabumi Shibuya

发明人： Kenya Shitara ,  Mikito Ito ,  Nobuo Hanai ,  Yoko Kawada ,  Kazuyasu Nakamura ,  Masabumi Shibuya

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

CPC分类号： G01N33/57407 ,  A61K38/00 ,  C07K16/2803 ,  C07K16/2863 ,  C07K2317/24 ,  C12N2799/026 ,  G01N33/6863 ,  G01N33/6893 ,  G01N33/74

摘要： The present invention provides an antibody or peptide which immunologically reacts with human VEGF receptor Flt-1 and cells in which human VEGF receptor Flt-1 is expressed on the cell surface and an antibody or peptide which inhibits binding of human VEGF to human VEGF receptor Flt-1. It also provides a means for the diagnosis or treatment of diseases in which their morbid states progress by abnormal angiogenesis, such as proliferation or metastasis of solid tumors, arthritis in rheumatoid arthritis, diabetic retinopathy, retinopathy of prematurity, psoriasis, and the like.

摘要翻译： 本发明提供了与人VEGF受体Flt-1和细胞表面上表达人VEGF受体Flt-1的细胞免疫反应的抗体或肽，以及抑制人VEGF与人VEGF受体Flt结合的抗体或肽 -1。 它还提供了用于诊断或治疗其病态通过异常血管生成进行的疾病（例如实体瘤的增殖或转移，类风湿性关节炎中的关节炎，糖尿病性视网膜病，早产儿视网膜病，牛皮癣等）的手段。

公开(公告)号：US5939532A

公开(公告)日：1999-08-17

申请号：US483528

申请日：1995-06-07

申请人： Kazuyasu Nakamura ,  Masamichi Koike ,  Kenya Shitara ,  Nobuo Hanai ,  Yoshihisa Kuwana ,  Mamoru Hasegawa

发明人： Kazuyasu Nakamura ,  Masamichi Koike ,  Kenya Shitara ,  Nobuo Hanai ,  Yoshihisa Kuwana ,  Mamoru Hasegawa

IPC分类号： C07K16/18 ,  C07K16/46 ,  C12P21/08 ,  C07K16/00 ,  C12N5/00 ,  C12P21/06

CPC分类号： C07K16/18 ,  C07K16/464 ,  C07K2317/24 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/00

摘要： Chimeric human antibody expression vectors are constructed by inserting the antibody heavy chain variable region-encoding cDNA and antibody light chain variable region-encoding cDNA isolated from hybridomas producing a mouse or rat monoclonal antibody reacting with the ganglioside GM.sub.2 respectively into an expression vector for use in animal cells which contains the human antibody heavy chain constant region- or human antibody light chain constant region-encoding cDNA. The expression vectors are introduced into animal cells and the transformant thus obtained is cultured for the production of a chimeric human antibody reacting with the ganglioside GM.sub.2. In contrast to mouse monoclonal antibodies, the chimeric human antibodies of the invention will not cause anti-mouse immunoglobulin antibody production in the patient's body but shows a prolonged blood half-life, with a reduced frequency of adverse effects, so that it can be expected to be superior to mouse monoclonal antibodies in the efficacy in the treatment of human cancer, for instance.

公开(公告)号：US20100092997A1

公开(公告)日：2010-04-15

申请号：US12550160

申请日：2009-08-28

申请人： Kazuyasu Nakamura ,  Kenya Shitara

发明人： Kazuyasu Nakamura ,  Kenya Shitara

IPC分类号： G01N33/53 ,  C07K16/00 ,  G01N33/566 ,  C12N5/10 ,  C12N1/16 ,  C12P21/04

CPC分类号： C12P21/02 ,  A61K39/395 ,  C07K16/22 ,  C07K16/283 ,  C07K16/2866 ,  C07K16/3084 ,  C07K2317/24 ,  C07K2317/41 ,  C07K2317/732 ,  C07K2319/30

摘要： A method for enhancing a binding activity of an antibody composition to Fcγ receptor IIIa, which comprises modifying a complex N-glycoside-linked sugar chain which is bound to the Fc region of an antibody molecule; a method for enhancing an antibody-dependent cell-mediated cytotoxic activity of an antibody composition; a process for producing an antibody composition having an enhanced binding activity to Fcγ receptor IIIa; a method for detecting the ratio of a sugar chain in which fucose is not bound to N-acetylglucosamine in the reducing end in the sugar chain among total complex N-glycoside-linked sugar chains bound to the Fc region in an antibody composition; an Fc fusion protein composition produced by using a cell resistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α-bond in a complex N-glycoside-linked sugar chain; and a process for producing the same.

摘要翻译： 一种增强抗体组合物与Fcγ受体IIIa的结合活性的方法，其包括修饰与抗体分子的Fc区结合的复合N-糖苷连接的糖链; 用于增强抗体依赖性细胞介导的抗体组合物的细胞毒活性的方法; 制备对Fcγ受体IIIa具有增强的结合活性的抗体组合物的方法; 在抗体组合物中与Fc区结合的总复合N-糖苷连接的糖链中，检测糖链与还原末端中的岩藻糖不与N-乙酰葡糖胺结合的糖链的比例的方法; 通过使用对凝集素有抗性的细胞产生的Fc融合蛋白质组合物，所述细胞通过复合N-糖苷中的α-键识别糖链的1-位与还原末端的N-乙酰葡糖胺的6-位结合的糖链 链糖链 及其制造方法。

公开(公告)号：US20060034838A1

公开(公告)日：2006-02-16

申请号：US11250411

申请日：2005-10-17

申请人： Kenya Shitara ,  Mikito Ito ,  Nobuo Hanai ,  Yoko Kawada ,  Kazuyasu Nakamura ,  Masabumi Shibuya

发明人： Kenya Shitara ,  Mikito Ito ,  Nobuo Hanai ,  Yoko Kawada ,  Kazuyasu Nakamura ,  Masabumi Shibuya

IPC分类号： A61K39/395

CPC分类号： G01N33/57407 ,  A61K38/00 ,  C07K16/2803 ,  C07K16/2863 ,  C07K2317/24 ,  C12N2799/026 ,  G01N33/6863 ,  G01N33/6893 ,  G01N33/74

摘要： The present invention provides an antibody or peptide which immunologically reacts with human VEGF receptor Flt-1 and cells in which human VEGF receptor Flt-1 is expressed on the cell surface and an antibody or peptide which inhibits binding of human VEGF to human VEGF receptor Flt-1. It also provides a means for the diagnosis or treatment of diseases in which their morbid states progress by abnormal angiogenesis, such as proliferation or metastasis of solid tumors, arthritis in rheumatoid arthritis, diabetic retinopathy, retinopathy of prematurity, psoriasis, and the like.

公开(公告)号：US06986890B1

公开(公告)日：2006-01-17

申请号：US09453718

申请日：1999-12-03

申请人： Kenya Shitara ,  Mikito Ito ,  Nobuo Hanai ,  Yoko Kawada ,  Kazuyasu Nakamura ,  Masabumi Shibuya

发明人： Kenya Shitara ,  Mikito Ito ,  Nobuo Hanai ,  Yoko Kawada ,  Kazuyasu Nakamura ,  Masabumi Shibuya

IPC分类号： A61K39/395

CPC分类号： G01N33/57407 ,  A61K38/00 ,  C07K16/2803 ,  C07K16/2863 ,  C07K2317/24 ,  C12N2799/026 ,  G01N33/6863 ,  G01N33/6893 ,  G01N33/74

摘要： The present invention provides an antibody or peptide which immunologically reacts with human VEGF receptor Flt-1 and cells in which human VEGF receptor Flt-1 is expressed on the cell surface and an antibody or peptide which inhibits binding of human VEGF to human VEGF receptor Flt-1. It also provides a means for the diagnosis or treatment of diseases in which their morbid states progress by abnormal angiogenesis, such as proliferation or metastasis of solid tumors, arthritis in rheumatoid arthritis, diabetic retinopathy, retinopathy of prematurity, psoriasis, and the like.

公开(公告)号：US06872392B2

公开(公告)日：2005-03-29

申请号：US10195752

申请日：2002-07-16

申请人： Kazuyasu Nakamura ,  Masamichi Koike ,  Kenya Shitara ,  Nobuo Hanai ,  Yoshihisa Kuwana ,  Mamoru Hasegawa

发明人： Kazuyasu Nakamura ,  Masamichi Koike ,  Kenya Shitara ,  Nobuo Hanai ,  Yoshihisa Kuwana ,  Mamoru Hasegawa

IPC分类号： A61K38/00 ,  A61P35/00 ,  C07K16/18 ,  C07K16/46 ,  C12P21/04 ,  C12P21/08 ,  A61K39/395 ,  A61K39/40 ,  A61K39/42 ,  C07K16/00

CPC分类号： C07K16/3084 ,  A61K38/00 ,  C07K16/18 ,  C07K16/464 ,  C07K2317/24 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/00 ,  Y10S530/867

摘要： Chimeric human antibody expression vectors are constructed by inserting the heavy chain variable region-encoding cDNA and antibody light chain variable region-encoding cDNA isolated from hybridomas producing a mouse or rat monoclonal antibody reacting with the ganglioside GM2 respectively into an expression vector which contains the human antibody heavy chain constant region- or human antibody light chain constant region-encoding cDNA. The expression vectors are introduced into animal cells and the transformant thus obtained is cultured to produce a chimeric human antibody reacting with the ganglioside GM2. In contrast to mouse monoclonal antibodies, the chimeric human antibodies of the invention will not cause anti-mouse immunoglobulin antibody production in the patient's body but show a prolonged blood half-life, with a reduced frequency of adverse effects, so that it can be expected to be superior to mouse monoclonal antibodies in the efficacy in the treatment of human cancer, for instance.

摘要翻译： 通过将分离自产生与神经节苷脂GM2反应的小鼠或大鼠单克隆抗体的杂交瘤的杂交瘤分离的重链可变区编码cDNA和抗体轻链可变区编码cDNA分别插入含有人类的表达载体来构建嵌合人抗体表达载体 抗体重链恒定区或人抗体轻链恒定区编码cDNA。 将表达载体导入动物细胞中，培养由此获得的转化体以产生与神经节苷脂GM2反应的嵌合人抗体。 与小鼠单克隆抗体相反，本发明的嵌合人抗体不会引起患者体内的抗小鼠免疫球蛋白抗体的产生，但是显示出延长的血液半衰期，并且有不利影响的频率降低，从而可以预期 例如，在治疗人类癌症的功效方面优于小鼠单克隆抗体。