公开(公告)号：EP3617313A1

公开(公告)日：2020-03-04

申请号：EP19186598.9

申请日：2012-10-05

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： IGAWA, Tomoyuki ,  TAMBA, Shigero ,  KAWAZOE, Meiri

IPC分类号： C12N15/09 ,  A61K39/00 ,  A61K39/395 ,  C07K16/18 ,  C12P21/02 ,  C12P21/08 ,  C12Q1/02

摘要： Disclosed are an antigen-binding molecule containing a sugar chain receptor-binding domain and having a weak antigen-binding activity in the pH of early-stage endosome compared to the antigen-binding activity in the pH of plasma; a pharmaceutical composition containing the antigen-binding molecule; and a method for producing these. Use of the antigen-binding molecule of the invention enables to promote uptake of an antigen into a cell and increase the number of antigens that a single antibody molecule can bind. Administration of the antibody enables to reduce the number of antigens in plasma more and more and improve pharmacokinetics of the antibody.

公开(公告)号：EP2813568A1

公开(公告)日：2014-12-17

申请号：EP13746387.3

申请日：2013-02-08

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： KURAMOCHI, Taichi ,  KAWAZOE, Meiri ,  MIMOTO, Futa ,  MAEDA, Atsuhiko ,  IGAWA, Tomoyuki

IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K39/395 ,  A61P1/04 ,  A61P3/06 ,  A61P3/10 ,  A61P7/00 ,  A61P7/06 ,  A61P9/10 ,  A61P11/00 ,  A61P11/02 ,  A61P11/06 ,  A61P13/12 ,  A61P15/08 ,  A61P17/00 ,  A61P17/06 ,  A61P19/00 ,  A61P19/10 ,  A61P25/00 ,  A61P29/00

CPC分类号： C07K16/28 ,  C07K16/00 ,  C07K16/2866 ,  C07K16/303 ,  C07K2317/52 ,  C07K2317/524 ,  C07K2317/94

摘要： Polypeptides with improved stability as compared to that of a parent polypeptide were successfully obtained by modifying at least one amino acid in a loop region of the antibody Fc region. Furthermore, by combining multiple amino acid modifications in the loop region, polypeptides with maintained or enhanced FcγR-binding activity as well as improved thermal stability, polypeptides with decreased FcγR-binding activity as well as improved thermal stability, and polypeptides with not only improved thermal stability and adjusted FcγR-binding activity but also decreased aggregate content, as compared to those of a parent polypeptide, were successfully obtained.

摘要翻译： 通过修饰抗体Fc区的环区域中的至少一个氨基酸，成功地获得了与母体多肽相比具有改善的稳定性的多肽。 此外，通过在环区域中组合多个氨基酸修饰，具有维持或增强的FcγR结合活性的多肽以及改善的热稳定性，具有降低的FcγR结合活性以及改善的热稳定性的多肽，以及不仅具有改善的热稳定性 与母体多肽相比，稳定性和调节的FcγR结合活性也降低了聚集体含量。

公开(公告)号：EP2765192A1

公开(公告)日：2014-08-13

申请号：EP12838341.1

申请日：2012-10-05

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： IGAWA, Tomoyuki ,  TAMBA, Shigero ,  KAWAZOE, Meiri

IPC分类号： C12N15/09 ,  A61K39/00 ,  A61K39/395 ,  C07K16/18 ,  C12P21/02 ,  C12P21/08 ,  C12Q1/02

CPC分类号： C07K16/28 ,  C07K16/283 ,  C07K2317/31 ,  C07K2317/41 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2317/94 ,  C12N15/1034

摘要： Disclosed are an antigen-binding molecule containing a sugar chain receptor-binding domain and having a weak antigen-binding activity in the pH of early-stage endosome compared to the antigen-binding activity in the pH of plasma; a pharmaceutical composition containing the antigen-binding molecule; and a method for producing these. Use of the antigen-binding molecule of the invention enables to promote uptake of an antigen into a cell and increase the number of antigens that a single antibody molecule can bind. Administration of the antibody enables to reduce the number of antigens in plasma more and more and improve pharmacokinetics of the antibody.

摘要翻译： 本发明公开了在含有的糖链受体结合结构域和具有在早期的pH的弱抗原结合活性核内体相比于血浆的pH抗原结合活性的抗原结合分子; 含有抗原结合分子的药物组合物; 和用于产生合成的方法。 本发明的抗原结合分子的使用使得以促进抗原的摄取到细胞中，并增加抗原没有单一抗体分子可结合的数量。 给予该抗体能够降低血浆中越来越多的抗原的数量，提高抗体的药物动力学。

公开(公告)号：EP2787078B1

公开(公告)日：2019-05-22

申请号：EP12846665.3

申请日：2012-10-31

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： KURAMOCHI, Taichi ,  KAWAZOE, Meiri ,  HIRONIWA, Naoka ,  IGAWA, Tomoyuki

IPC分类号： C07K16/28 ,  C07K16/00 ,  C07K16/30 ,  C07K16/46

公开(公告)号：EP2728002A1

公开(公告)日：2014-05-07

申请号：EP12804446.8

申请日：2012-06-29

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： MIMOTO, Futa ,  KURAMOCHI, Taichi ,  IGAWA, Tomoyuki ,  KAWAZOE, Meiri ,  KATADA, Hitoshi ,  SHIRAIWA, Hirotake ,  KADONO, Shojiro

IPC分类号： C12N15/09 ,  A61K39/395 ,  C07K16/28 ,  C07K16/46

CPC分类号： C07K16/46 ,  C07K1/1075 ,  C07K16/00 ,  C07K16/18 ,  C07K16/22 ,  C07K16/2866 ,  C07K16/30 ,  C07K16/303 ,  C07K16/36 ,  C07K2317/52 ,  C07K2317/524 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/732 ,  C07K2317/92 ,  C07K2317/94 ,  G01N33/566

摘要： The present inventors produced a heterodimerized polypeptide having an Fc region formed from two polypeptides with different amino acid sequences (a first polypeptide and a second polypeptide), and succeeded in producing a heterodimerized polypeptide containing an Fc region with improved Fc region function compared to that of a homodimer in which the Fc region is composed of only the first polypeptide or only the second polypeptide by conventional technology.

摘要翻译： 本发明人产生了具有由具有不同氨基酸序列的两个多肽（第一多肽和第二多肽）形成的Fc区的异二聚体多肽，并且成功地产生含有具有改善的Fc区功能的Fc区的异二聚化多肽， 其中Fc区由常规技术仅由第一多肽或仅第二多肽组成的同二聚体。

公开(公告)号：EP4011913A1

公开(公告)日：2022-06-15

申请号：EP21195522.4

申请日：2012-06-29

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： MIMOTO, Futa ,  KURAMOCHI, Taichi ,  IGAWA, Tomoyuki ,  KAWAZOE, Meiri ,  KATADA, Hitoshi ,  SHIRAIWA, Hirotake ,  KADONO, Shojiro

IPC分类号： C07K16/28 ,  C07K16/46 ,  C07K16/00 ,  C07K16/18 ,  C07K16/30 ,  C07K16/36 ,  A61K39/395 ,  C12N15/09

摘要： The present inventors produced a heterodimerized polypeptide having an Fc region formed from two polypeptides with different amino acid sequences (a first polypeptide and a second polypeptide), and succeeded in producing a heterodimerized polypeptide containing an Fc region with improved Fc region function compared to that of a homodimer in which the Fc region is composed of only the first polypeptide or only the second polypeptide by conventional technology.

公开(公告)号：EP3805757A1

公开(公告)日：2021-04-14

申请号：EP19814338.0

申请日：2019-06-03

申请人： CHUGAI SEIYAKU KABUSHIKI KAISHA

发明人： NAOI, Sotaro ,  KAWAZOE, Meiri

IPC分类号： G01N33/53 ,  G01N33/543

摘要： The present invention provides methods for detecting a complex with low affinity, under conditions in which the binding equilibrium of the complex is substantially maintained, and methods for measuring the concentration and/or amount of the complex. The invention also provides methods for evaluating the kinetics of a complex and methods for deciding on a therapeutic method that uses a pharmaceutical agent, based on the concentration and/or amount of the complex determined by the above-mentioned measurement method.

公开(公告)号：EP2787078A1

公开(公告)日：2014-10-08

申请号：EP12846665.3

申请日：2012-10-31

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： KURAMOCHI, Taichi ,  KAWAZOE, Meiri ,  HIRONIWA, Naoka ,  IGAWA, Tomoyuki

IPC分类号： C12N15/09 ,  A61K39/395 ,  C07K16/46 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12P21/02 ,  C12P21/08

CPC分类号： C07K16/00 ,  C07K16/2866 ,  C07K16/303 ,  C07K16/468 ,  C07K2317/31 ,  C07K2317/522

摘要： It was found that association between CH1 and CL can be suppressed by substituting amino acids that exist on the interface between CH1 and CL with electrically-charged amino acids, and that formation of heterogeneous molecules is enabled more efficiently than by introducing knobs into holes mutations into CH3 domain.

摘要翻译： 发现CH1和CL之间的关联可以通过用存在于带有电荷氨基酸的CH1和CL之间的界面上的氨基酸来抑制，并且通过将孔插入孔突变中能够更有效地形成异质分子 CH3结构域。