-
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。
-
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。
-
公开(公告)号：US20110098450A1
公开(公告)日：2011-04-28
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
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。
-
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。
-
-
-
搜索结果
4 条记录 (耗时 0.017 秒)
