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公开(公告)号：US09340615B2
公开(公告)日：2016-05-17
申请号：US13320317
申请日：2010-05-14
申请人： Atsuhiko Maeda , Hajime Miyamoto , Taichi Kuramochi , Atsushi Matsuo , Tomoyuki Igawa , Hirotake Shiraiwa , Hiroyuki Tsunoda , Tatsuhiko Tachibana
发明人： Atsuhiko Maeda , Hajime Miyamoto , Taichi Kuramochi , Atsushi Matsuo , Tomoyuki Igawa , Hirotake Shiraiwa , Hiroyuki Tsunoda , Tatsuhiko Tachibana
CPC分类号： C07K16/2863 , A61K2039/505 , C07K16/303 , C07K2317/24 , C07K2317/30 , C07K2317/76 , C07K2317/92
摘要： An objective of the present invention is to decrease the immunogenicity of mouse-derived anti-AXL antibodies in humans by humanizing them. The present invention provides antibodies that can bind to a specific region in Anexelekto (AXL) and humanized antibodies that are produced based on such antibodies. The anti-AXL antibodies of the present invention have high antitumor activity, and are useful as agents for decreasing the AXL expression level, antitumor agents, and diagnostic agents for cancer.
摘要翻译： 本发明的目的是通过人源化来降低小鼠来源的抗AXL抗体在人体中的免疫原性。 本发明提供可以结合Anexelekto（AXL）中的特定区域的抗体和基于此类抗体产生的人源化抗体。 本发明的抗AXL抗体具有高抗肿瘤活性，可用作降低AXL表达水平的药剂，抗肿瘤剂和癌症诊断剂。
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公开(公告)号：US20120121587A1
公开(公告)日：2012-05-17
申请号：US13320317
申请日：2010-05-14
申请人： Atsuhiko Maeda , Hajime Miyamoto , Taichi Kuramochi , Atsushi Matsuo , Tomoyuki Igawa , Hirotake Shiraiwa , Hiroyuki Tsunoda , Tatsuhiko Tachibana
发明人： Atsuhiko Maeda , Hajime Miyamoto , Taichi Kuramochi , Atsushi Matsuo , Tomoyuki Igawa , Hirotake Shiraiwa , Hiroyuki Tsunoda , Tatsuhiko Tachibana
IPC分类号： A61K39/395 , A61P35/00 , C07K16/28
CPC分类号： C07K16/2863 , A61K2039/505 , C07K16/303 , C07K2317/24 , C07K2317/30 , C07K2317/76 , C07K2317/92
摘要： An objective of the present invention is to decrease the immunogenicity of mouse-derived anti-AXL antibodies in humans by humanizing them. The present invention provides antibodies that can bind to a specific region in Anexelekto (AXL) and humanized antibodies that are produced based on such antibodies. The anti-AXL antibodies of the present invention have high antitumor activity, and are useful as agents for decreasing the AXL expression level, antitumor agents, and diagnostic agents for cancer.
摘要翻译： 本发明的目的是通过人源化来降低小鼠来源的抗AXL抗体在人体中的免疫原性。 本发明提供可以结合Anexelekto（AXL）中的特定区域的抗体和基于此类抗体产生的人源化抗体。 本发明的抗AXL抗体具有高抗肿瘤活性，可用作降低AXL表达水平的药剂，抗肿瘤剂和癌症诊断剂。
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公开(公告)号：US08575317B2
公开(公告)日：2013-11-05
申请号：US12809138
申请日：2009-12-04
申请人： Taichi Kuramochi , Keiko Kasutani , Souhei Ohyama , Hiroyuki Tsunoda , Tomoyuki Igawa , Tatsuhiko Tachibana , Hirotake Shiraiwa , Keiko Esaki
发明人： Taichi Kuramochi , Keiko Kasutani , Souhei Ohyama , Hiroyuki Tsunoda , Tomoyuki Igawa , Tatsuhiko Tachibana , Hirotake Shiraiwa , Keiko Esaki
CPC分类号： C07K16/2866 , A61K2039/505 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , G01N33/6869 , G01N2333/7155
摘要： The present inventors successfully obtained anti-NR10 antibodies having an effective neutralizing activity against NR10. The anti-NR10 antibodies provided by the present invention are useful as, for example, pharmaceuticals for treating or preventing inflammatory diseases.
摘要翻译： 本发明人成功获得了抗NR10抗体的抗NR10抗体。 本发明提供的抗NR10抗体可用作例如用于治疗或预防炎性疾病的药物。
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公开(公告)号：US20110229459A1
公开(公告)日：2011-09-22
申请号：US12809138
申请日：2009-12-04
申请人： Taichi Kuramochi , Keiko Kasutani , Souhei Ohyama , Hiroyuki Tsunoda , Tomoyuki Igawa , Tatsuhiko Tachibana , Hirotake Shiraiwa , Keiko Esaki
发明人： Taichi Kuramochi , Keiko Kasutani , Souhei Ohyama , Hiroyuki Tsunoda , Tomoyuki Igawa , Tatsuhiko Tachibana , Hirotake Shiraiwa , Keiko Esaki
IPC分类号： A61K39/395 , C07K16/28 , A61P29/00
CPC分类号： C07K16/2866 , A61K2039/505 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , G01N33/6869 , G01N2333/7155
摘要： The present inventors successfully obtained anti-NR10 antibodies having an effective neutralizing activity against NR10. The anti-NR10 antibodies provided by the present invention are useful as, for example, pharmaceuticals for treating or preventing inflammatory diseases.
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公开(公告)号：US08497355B2
公开(公告)日：2013-07-30
申请号：US12733933
申请日：2008-09-26
申请人： Tomoyuki Igawa , Taichi Kuramochi , Hirotake Shiraiwa , Hiroyuki Tsunoda , Tatsuhiko Tachibana , Takahiro Ishiguro
发明人： Tomoyuki Igawa , Taichi Kuramochi , Hirotake Shiraiwa , Hiroyuki Tsunoda , Tatsuhiko Tachibana , Takahiro Ishiguro
IPC分类号： C07K16/30 , A61K39/395 , C07H21/04 , C12P21/08 , C12N15/13
CPC分类号： C07K16/2863 , A61K2039/505 , A61K2039/545 , C07K16/18 , C07K16/30 , C07K16/303 , C07K2317/14 , C07K2317/56 , C07K2317/73 , C07K2317/732 , C07K2317/92 , C07K2317/94 , C12N15/8258
摘要： A method of modulating the plasma half-life of anti-glypican 3 antibody, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody that has a plasma half-life that has been modulated, a method of preparing the anti-glypican 3 antibody and a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient are provided. Disclosed is a method of modulating the plasma half-life of anti-glypican 3 antibody by modifying an amino acid residue that is exposed on the surface of the anti-glypican 3 antibody; and anti-glypican 3 antibody that has a plasma half-life that has been modulated by amino acid residue modification, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody, and a method of preparing the anti-glypican 3 antibody and producing a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient.
摘要翻译： 调节抗磷脂酰肌醇蛋白聚糖3抗体的血浆半衰期的方法，一种药物组合物，其包含具有调节的血浆半衰期的抗磷脂酰肌醇蛋白聚糖3抗体作为活性成分，制备抗磷脂酰肌醇蛋白聚糖的方法 提供了包含抗磷脂酰肌醇蛋白聚糖3抗体作为活性成分的药物组合物。 公开了通过改变暴露于抗磷脂酰肌醇蛋白聚糖3抗体表面的氨基酸残基来调节抗磷脂酰肌醇蛋白聚糖3抗体的血浆半衰期的方法; 和具有通过氨基酸残基修饰调节的血浆半衰期的抗磷脂酰肌醇蛋白聚糖3抗体，包含作为活性成分的磷脂酰肌醇蛋白聚糖3抗体的药物组合物，以及制备抗磷脂酰肌醇蛋白聚糖3抗体的方法和 制备包含抗磷脂酰肌醇蛋白聚糖3抗体作为活性成分的药物组合物。
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公开(公告)号：US20110129459A1
公开(公告)日：2011-06-02
申请号：US12745781
申请日：2008-12-05
申请人： Taichi Kuramochi , Keiko Kasutani , Souhei Ohyama , Hiroyuki Tsunoda , Tomoyuki Igawa , Tatsuhiko Tachibana , Hirotake Shiraiwa , Keiko Esaki
发明人： Taichi Kuramochi , Keiko Kasutani , Souhei Ohyama , Hiroyuki Tsunoda , Tomoyuki Igawa , Tatsuhiko Tachibana , Hirotake Shiraiwa , Keiko Esaki
IPC分类号： A61K39/395 , C07K16/18 , A61P29/00
CPC分类号： C07K16/2866 , A61K2039/505 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , G01N33/6869 , G01N2333/7155
摘要： The present inventors successfully obtained anti-NR10 antibodies having an effective neutralizing activity against NR10. The anti-NR10 antibodies provided by the present invention are useful as, for example, pharmaceuticals for treating or preventing inflammatory diseases.
摘要翻译： 本发明人成功获得了抗NR10抗体的抗NR10抗体。 本发明提供的抗NR10抗体可用作例如用于治疗或预防炎性疾病的药物。
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公开(公告)号：US20100239577A1
公开(公告)日：2010-09-23
申请号：US12733933
申请日：2008-09-26
申请人： Tomoyuki Igawa , Taichi Kuramochi , Hirotake Shiraiwa , Hiroyuki Tsunoda , Tatsuhiko Tachibana , Takahiro Ishiguro
发明人： Tomoyuki Igawa , Taichi Kuramochi , Hirotake Shiraiwa , Hiroyuki Tsunoda , Tatsuhiko Tachibana , Takahiro Ishiguro
CPC分类号： C07K16/2863 , A61K2039/505 , A61K2039/545 , C07K16/18 , C07K16/30 , C07K16/303 , C07K2317/14 , C07K2317/56 , C07K2317/73 , C07K2317/732 , C07K2317/92 , C07K2317/94 , C12N15/8258
摘要： A method of modulating the plasma half-life of anti-glypican 3 antibody, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody that has a plasma half-life that has been modulated, a method of preparing the anti-glypican 3 antibody and a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient are provided. Disclosed is a method of modulating the plasma half-life of anti-glypican 3 antibody by modifying an amino acid residue that is exposed on the surface of the anti-glypican 3 antibody; and anti-glypican 3 antibody that has a plasma half-life that has been modulated by amino acid residue modification, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody, and a method of preparing the anti-glypican 3 antibody and producing a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient.
摘要翻译： 调节抗磷脂酰肌醇蛋白聚糖3抗体的血浆半衰期的方法，一种药物组合物，其包含具有调节的血浆半衰期的抗磷脂酰肌醇蛋白聚糖3抗体作为活性成分，制备抗磷脂酰肌醇蛋白聚糖的方法 提供了包含抗磷脂酰肌醇蛋白聚糖3抗体作为活性成分的药物组合物。 公开了通过改变暴露于抗磷脂酰肌醇蛋白聚糖3抗体表面的氨基酸残基来调节抗磷脂酰肌醇蛋白聚糖3抗体的血浆半衰期的方法; 和具有通过氨基酸残基修饰调节的血浆半衰期的抗磷脂酰肌醇蛋白聚糖3抗体，包含作为活性成分的磷脂酰肌醇蛋白聚糖3抗体的药物组合物，以及制备抗磷脂酰肌醇蛋白聚糖3抗体的方法和 制备包含抗磷脂酰肌醇蛋白聚糖3抗体作为活性成分的药物组合物。
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公开(公告)号：US20120253016A1
公开(公告)日：2012-10-04
申请号：US13524528
申请日：2012-06-15
申请人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Mika Sakurai , Tetsuo Kojima , Tatsuhiko Tachibana , Hirotake Shiraiwa , Hiroyuki Tsunoda , Yoshinobu Higuchi
发明人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Mika Sakurai , Tetsuo Kojima , Tatsuhiko Tachibana , Hirotake Shiraiwa , Hiroyuki Tsunoda , Yoshinobu Higuchi
CPC分类号： C07K16/2866 , A61K39/00 , A61K2039/505 , C07K16/461 , C07K2317/24 , C07K2317/41 , C07K2317/76 , C07K2317/92
摘要： The present invention provides pharmaceutical compositions comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. The present invention also provides methods for producing these pharmaceutical compositions. The present inventors have successfully generated second-generation molecules that are superior to TOCILIZUMAB by appropriately combining amino acid sequence alterations in the CDR domains, variable regions, and constant regions.
摘要翻译： 本发明通过改变作为人源化抗IL-6受体IgG1抗体的TOCILIZUMAB的可变区和恒定区的氨基酸序列来提供优于TOCILIZUMAB的第二代分子的药物组合物，以增强抗原 - 中和能力增强，药代动力学改善，治疗效果较差，免疫原性，安全性和物理化学性质（稳定性和均一性）均有改善。 本发明还提供了制备这些药物组合物的方法。 通过适当地组合CDR结构域，可变区和恒定区中的氨基酸序列改变，本发明人成功地生产出优于TOCILIZUMAB的第二代分子。
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公开(公告)号：US08562991B2
公开(公告)日：2013-10-22
申请号：US12680087
申请日：2009-09-25
申请人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Mika Sakurai , Tetsuo Kojima , Tatsuhiko Tachibana , Hirotake Shiraiwa , Hiroyuki Tsunoda , Yoshinobu Higuchi
发明人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Mika Sakurai , Tetsuo Kojima , Tatsuhiko Tachibana , Hirotake Shiraiwa , Hiroyuki Tsunoda , Yoshinobu Higuchi
IPC分类号： A61K39/395
CPC分类号： C07K16/2866 , A61K39/00 , A61K2039/505 , C07K16/461 , C07K2317/24 , C07K2317/41 , C07K2317/76 , C07K2317/92
摘要： The present invention provides pharmaceutical compositions comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. The present invention also provides methods for producing these pharmaceutical compositions. The present inventors have successfully generated second-generation molecules that are superior to TOCILIZUMAB by appropriately combining amino acid sequence alterations in the CDR domains, variable regions, and constant regions.
摘要翻译： 本发明通过改变作为人源化抗IL-6受体IgG1抗体的TOCILIZUMAB的可变区和恒定区的氨基酸序列来提供优于TOCILIZUMAB的第二代分子的药物组合物，以增强抗原 - 中和能力增强，药代动力学改善，治疗效果较差，免疫原性，安全性和物理化学性质（稳定性和均一性）均有改善。 本发明还提供了制备这些药物组合物的方法。 通过适当地组合CDR结构域，可变区和恒定区中的氨基酸序列改变，本发明人成功地生产出优于TOCILIZUMAB的第二代分子。
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公开(公告)号：US20110245473A1
公开(公告)日：2011-10-06
申请号：US12680112
申请日：2008-09-26
申请人： Tomoyuki Igawa , Mika Sakurai , Tetsuo Kojima , Tatsuhiko Tachibana , Hirotake Shiraiwa , Hiroyuki Tsunoda , Atsuhiko Maeda
发明人： Tomoyuki Igawa , Mika Sakurai , Tetsuo Kojima , Tatsuhiko Tachibana , Hirotake Shiraiwa , Hiroyuki Tsunoda , Atsuhiko Maeda
IPC分类号： C07K16/28
CPC分类号： C07K16/2866 , A61K2039/505 , C07K2317/24 , C07K2317/53 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , G01N33/6854 , G01N33/6869 , G01N2333/7155 , G01N2500/04 , G01N2500/10
摘要： The present inventors succeeded in discovering specific amino acid mutations in the variable region, framework region, and constant region of TOCILIZUMAB, and this enables to reduce immunogenicity risk and the heterogeneity originated from disulfide bonds in the hinge region, as well as to improve antigen binding activity, pharmacokinetics, stability under acidic conditions, and stability in high concentration preparations.
摘要翻译： 本发明人成功地发现了TOCILIZUMAB的可变区，框架区和恒定区中的特异性氨基酸突变，这使得能够降低源自铰链区的二硫键的免疫原性风险和异质性，并且改善抗原结合 活性，药代动力学，酸性条件下的稳定性和高浓度制剂中的稳定性。
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